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1.
J Clin Lab Anal ; 35(3): e23695, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33543811

RESUMO

Anti-human globulin (AHG) reagents are widely applied in pretransfusion compatibility tests. The accuracy of detection with AHG reagents is mainly affected by irregular antibodies or cold agglutinins in blood samples, which are related to the human complement system. Although much has been written about various types and applications of AHG reagents, their characteristics, interference factors and optimal selection in pretransfusion compatibility tests still need to be further clarified. Here, we review clinical practice and basic studies that describe each AHG reagent, summarize the advantages and disadvantages of using different AHG reagents in the presence of cold agglutinins or complement-fixing antibodies, explore the potential mechanisms by which the complement system influences detection with AHG reagents and address the question of how to optimally select AHG reagents for clinically significant antibody detection.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas/métodos , Indicadores e Reagentes , Soroglobulinas/imunologia , Aglutininas , Teste de Coombs , Humanos , Imunoglobulina G/imunologia
2.
Vet Immunol Immunopathol ; 220: 109987, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31790920

RESUMO

Conglutinin, a liver synthesized versatile innate immune marker consisting C-type lectin domain belongs to collectin superfamily of proteins. The protein, first detected in bovine serum as soluble pattern recognition receptor (PRR) has wide range of antimicrobial activities. In the present study, open reading frame (ORF) encoding neck and carbohydrate recognition domain (NCRD) of goat conglutinin gene ligated to the vector pRSET-A was expressed in E. coli BL-21(pLys) cells. The 27 kDa recombinant protein (rGCGN) purified by single step Ni+2 -NTA affinity chromatography was found to cross-react with recombinant anti-buffalo conglutinin antibody raised in poultry. Further, it displayed calcium-dependant sugar binding activity towards yeast mannan and calcium-independent binding activity towards LPS. The mannan binding activity of rGCGN was inhibited in the presence of N-acetyl-glucosamine because of higher affinity towards this sugar. The recombinant protein was found to stimulate production of superoxide ions and hydrogen peroxide in goat neutrophils, which are instrumental in stimulating phagocytic activity of cells. When used as antigen in Sandwich ELISA, straight line (Y = 0.299x + 0.067, R2 = 0.997) was observed within the concentration range of 200-1000 ng/100 µl of rGCGN. Using this equation, the native conglutinin concentration in goat sera was estimated to be 0.5-7.5 µg/ml. The results indicated that prokaryotically expressed functionally active rGCGN can be used as antigen to assess native serum conglutinin levels in Sandwich ELISA and as immunomodulator in therapeutic applications to sequester unwanted immune complexes from the circulation.


Assuntos
Colectinas/sangue , Colectinas/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Imunidade Inata , Fatores Imunológicos/imunologia , Soroglobulinas/imunologia , Animais , Biomarcadores , Colectinas/genética , Cabras , Fatores Imunológicos/genética , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Fagocitose , Espécies Reativas de Oxigênio/imunologia , Proteínas Recombinantes/imunologia , Soroglobulinas/genética
4.
Front Immunol ; 9: 3159, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30804949

RESUMO

Bovine conglutinin, the first animal collectin to be discovered, is structurally very similar to Surfactant Protein D (SP-D). SP-D is known to interact with Mycobacterium tuberculosis, and the closely-related M. bovis, the causative agent of bovine tuberculosis. We speculated that due to the overall similarities between conglutinin and SP-D, conglutinin is likely to have a protective influence in bovine tuberculosis. We set out to investigate the role of conglutinin in host-pathogen interaction during mycobacterial infection. We show here that a recombinant truncated form of conglutinin (rfBC), composed of the neck and C-type lectin domains, binds specifically and in a dose-dependent manner to the model organism Mycobacterium bovis BCG. rfBC showed a significant direct bacteriostatic effect on the growth of M. bovis BCG in culture. In addition, rfBC inhibited the uptake of M. bovis BCG by THP-1 macrophages (human monocyte lineage cell line) and suppressed the subsequent pro-inflammatory response. Conglutinin is well-known as a binder of the complement activation product, iC3b. rfBC was also able to inhibit the uptake of complement-coated M. bovis BCG by THP-1 macrophages, whilst modulating the pro-inflammatory response. It is likely that rfBC inhibits the phagocytosis of mycobacteria by two distinct mechanisms: firstly, rfBC interferes with mannose receptor-mediated uptake by masking lipoarabinomannan (LAM) on the mycobacterial surface. Secondly, since conglutinin binds iC3b, it can interfere with complement receptor-mediated uptake via CR3 and CR4, by masking interactions with iC3b deposited on the mycobacterial surface. rfBC was also able to modulate the downstream pro-inflammatory response in THP-1 cells, which is important for mobilizing the adaptive immune response, facilitating containment of mycobacterial infection. In conclusion, we show that conglutinin possesses complement-dependent and complement-independent anti-mycobacterial activities, interfering with both known mechanisms of mycobacterial uptake by macrophages. As mycobacteria are specialized intracellular pathogens, conglutinin may inhibit M. bovis and M. tuberculosis from establishing an intracellular niche within macrophages, and thus, negatively affect the long-term survival of the pathogen in the host.


Assuntos
Colectinas/imunologia , Proteínas do Sistema Complemento/imunologia , Mycobacterium bovis/imunologia , Soroglobulinas/imunologia , Tuberculose Bovina/imunologia , Tuberculose Bovina/microbiologia , Animais , Biomarcadores , Bovinos , Colectinas/metabolismo , Proteínas do Sistema Complemento/metabolismo , Citocinas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Fagocitose/imunologia , Soroglobulinas/metabolismo , Células THP-1 , Tuberculose Bovina/metabolismo
5.
Vet Parasitol Reg Stud Reports ; 12: 99-105, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-31014818

RESUMO

Originally described in cattle, conglutinin belongs to the collectin family and is involved in innate immune defense. It is thought that conglutinin provides the first line of defense by maintaining a symbiotic relationship with the microbes in the rumen while inhibiting inflammatory reactions caused by antibodies leaking into the bloodstream. Due to the lack of information on the similar lectins and sequence detection in goats, we characterized the goat conglutinin gene using RACE and evaluated the differences in its gene expression profile, as well as in the gene expression profiles for surfactant protein A, galectins 14 and 11, interleukin 4 and interferon-gamma in goats. We used Saanen and Anglo Nubian F2 crossbred goats monitored over a period of four months and characterized them as resistant (R) or susceptible (S) based on the average values of EPG counts. Goat conglutinin was similar to bovine conglutinin, but its gene expression varied among different tissues. However, as with bovine conglutinin, it was most highly expressed in the liver. Variation in conglutinin (R=24.3±3.9; S=23.5±2.6, p=0.059), protein surfactant A (R=23.8±5.2, S=24.4±2.3, p=0.16), galectin 14 (R=15.9±3.5, S=14.7±6.2, p=0.49) and galectin l1 gene expression (R=25.4±2.6, S=25.8±3.7, p=0.53) was not significant between groups. However, there were weak correlations between interleukin 4 and the protein surfactant A gene (r=0.459, p=0.02) and between interleukin 4 and galectin 11 (r=0.498, p=0.01). Strong correlation between interferon-gamma and galectin 14 (r=0.744, p=0.00) was observed. Galectin 14 was negatively correlated with the number of nematodes in the goat (r=-0.416, p=0.04) as well as the EPG count (r=-0.408, p=0.04). This is the first study to date that identifies the gene expression of conglutinin, surfactant protein A and galectins 14 and 11 in the goat abomasum. In conclusion, we present evidence that lectin is involved in the immune response to gastrointestinal nematodes, which suggests that collectins and galectins are involved in the molecular recognition of helminths.


Assuntos
Abomaso/imunologia , Colectinas/genética , Galectinas/genética , Doenças das Cabras/imunologia , Doenças das Cabras/parasitologia , Infecções por Nematoides/imunologia , Animais , Colectinas/imunologia , Resistência à Doença/imunologia , Feminino , Galectinas/imunologia , Gastroenteropatias/imunologia , Gastroenteropatias/parasitologia , Trato Gastrointestinal/parasitologia , Perfilação da Expressão Gênica , Cabras/parasitologia , Imunidade Inata , Interleucina-4/genética , Masculino , Proteína A Associada a Surfactante Pulmonar/genética , Reação em Cadeia da Polimerase em Tempo Real , Soroglobulinas/genética , Soroglobulinas/imunologia
6.
Anim Biotechnol ; 26(1): 29-36, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25153452

RESUMO

Conglutinin, a soluble pattern recognition receptor of innate immune system in bovines is known for its potential defensive activity against microorganisms either by direct agglutination in the presence of calcium or by acting as opsonin. In the present study, sheep (Ovis aries) conglutinin encoding neck and carbohydrate recognition domain (rSCGN) was expressed in the E coli BL21 expression host. The recombinant conglutinin revealed molecular weight of 27 kDa in SDS PAGE and also in western blotting using antibuffalo conglutinin polyclonal serum. The protein was characterized further for its functional activity in various assays. In ELISA based sugar and LPS binding assay, the rSCGN revealed its high binding activity toward N-acetyl glucosamine and E. coli LPS in the presence and the absence of calcium ions, respectively. Hemagglutination of chicken red blood cells caused by Newcastle disease virus was not inhibited in the presence of rSCGN as it lacked complete collagenous region present in the native protein. In virus neutralization test, the recombinant protein was found to reduce multiplication of bovine herpes virus-1 propagated in MDBK cells. This prokaryotically expressed 27 kDa recombinant sheep conglutinin can serve as antigen in future studies to develop sandwich ELISA for assessing the level of native conglutinin in sheep serum.


Assuntos
Colectinas/química , Colectinas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Soroglobulinas/química , Soroglobulinas/metabolismo , Acetilglucosamina/metabolismo , Animais , Galinhas , Colectinas/genética , Colectinas/imunologia , Eritrócitos/virologia , Escherichia coli , Lipopolissacarídeos/metabolismo , Vírus da Doença de Newcastle , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Soroglobulinas/genética , Soroglobulinas/imunologia , Carneiro Doméstico
7.
Ann Agric Environ Med ; 19(2): 221-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22742791

RESUMO

OBJECTIVE: Farming is associated with exposure to a wide variety of risk factors including organic dusts, endotoxins, allergens and other chemicals. The ability of some of these agents to interact with the immune system is demonstrated in the presented study which was undertaken to evaluate the relationship between pig and cow breeding, and the immune system early changes. Particular attention is paid to selected serum cytokines. METHODS: Sixty four animal breeders (36 cattle and 28 pig breeders) were selected as the exposed group, and 32 rural workers not engaged in animal breeding were utilised as the controls. Personal data were collected through a questionnaire, and selected serum parameters measured, including cytokines IL-6, IL-8, IL-10, IFNγ and TNFα, immunoglobulins and proteins, and total and differential white blood cell counts. RESULTS: The study stresses the significant increase of TNF-α, IL-8, and IL-10 in animal breeders, with the highest values in pig breeders, and a slight but statistically significant increase in albumin and total serum proteins. CONCLUSIONS: The findings of the presented study suggest a condition of immune system activation in animal breeders, with the highest levels observed in pig breeders. These changes may be attributable to exposure to organic dusts, endotoxins, or to the different biological agents present in the rural environment. The prognostic significance of these findings, however, remains unclear, but the observed changes might be indicative of a risk of developing respiratory toxic and allergic diseases, which need to be further investigated.


Assuntos
Albuminas/imunologia , Citocinas/imunologia , Exposição Ocupacional , Soroglobulinas/imunologia , Adulto , Idoso , Agricultura , Albuminas/metabolismo , Criação de Animais Domésticos , Animais , Contagem de Células Sanguíneas , Bovinos , Estudos Transversais , Citocinas/metabolismo , Eletroforese , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Soroglobulinas/metabolismo , Suínos , Adulto Jovem
8.
Fish Shellfish Immunol ; 30(3): 824-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21237272

RESUMO

Almost all metabolic processes in an organism alternate through high and low activity phases with a regular periodicity of nearly 24h. These daily/diel variations are governed by factors such as light, weather conditions, availability of food or predator activity. The immune system in fish is expected to follow the same routine based on external cues from the environment which it lives. The present study was carried out to investigate such daily/diel variations in selected immune parameters such as serum lysozyme and peroxidases activity, total serum globulin level and peripheral blood leukocyte count in Oreochromis mossambicus. The fish were maintained in semi natural condition (i.e.12L:12D). The results showed significant rise in serum peroxidases and lysozyme between 0200 h and 0600 h of the day and serum cortisol exhibited elevated level between 2200 h and 0600 h. Total serum globulin exhibited peak concentration from 1400 h to 1800 h. Thus suggesting the possibility of rhythmic functioning of immune system in O. mossambicus.


Assuntos
Ritmo Circadiano/imunologia , Tilápia/imunologia , Animais , Granulócitos/imunologia , Contagem de Leucócitos , Linfócitos/imunologia , Monócitos/imunologia , Muramidase/sangue , Muramidase/imunologia , Peroxidase/sangue , Peroxidase/imunologia , Soroglobulinas/imunologia , Tilápia/sangue
9.
Parasitol Res ; 108(1): 23-30, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20820805

RESUMO

In this study, we reported the first outbreak of the infection by Trypanosoma vivax in horses in southern Brazil, a non-endemic region where bovines have only recently been found infected by this trypanosome species. We evaluated 12 horses from a farm in southern Brazil, where four horses displayed pale mucous membranes, fever, weight loss, and swelling of abdomen, prepuce, or vulva. The diagnosis of T. vivax was confirmed in four horses by morphological parameters of trypomastigotes in blood smears and species-specific PCR. All T. vivax-infected animals showed anemia, and most showed increased levels of beta-1, beta-2, and gamma globulins. Horses were treated with diminazene aceturate, but cure was not achieved, and the disease relapsed after therapy. These findings demonstrated that Brazilian T. vivax isolates, which were already reported infecting cattle, buffaloes, goats, and sheep, can be highly pathogenic for horses, causing severe disease and even death of the animals due to the recurrence of the infection.


Assuntos
Surtos de Doenças , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/parasitologia , Cavalos/parasitologia , Trypanosoma vivax/isolamento & purificação , Tripanossomíase Africana/veterinária , Anemia/parasitologia , Anemia/patologia , Anemia/veterinária , Animais , Sangue/imunologia , Sangue/parasitologia , Brasil/epidemiologia , Doenças dos Cavalos/patologia , Soroglobulinas/análise , Soroglobulinas/imunologia , Tripanossomíase Africana/parasitologia , Tripanossomíase Africana/patologia
10.
Innate Immun ; 16(3): 131-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20529970

RESUMO

Soluble pattern-recognition innate immune proteins functionally resemble the antibodies of the adaptive immune system. Two major families of such proteins are ficolins and collectins or collagenous lectins (e.g. mannose-binding lectin [MBL], surfactant proteins [SP-A and SP-D] and conglutinin). In general, subunits of ficolins and collectins recognize the carbohydrate arrays of their targets via globular trimeric carbohydrate-recognition domains (CRDs) whereas IgG, IgM and other antibody isotypes recognize proteins via dimeric antigen-binding domains (Fab). Considering the structure and functions of these proteins, ficolins and MBL are analogous to molecules with the complement activating functions of C1q and the target recognition ability of IgG. Although the structure of SP-A is similar to MBL, it does not activate the complement system. Surfactant protein-D and conglutinin could be considered as the collagenous non-complement activating giant IgMs of the innate immune system. Proteins such as peptidoglycan-recognition proteins, pentraxins and agglutinin gp-340/DMBT1 are also pattern-recognition proteins. These proteins may be considered as different isotypes of antibody-like molecules. Proteins such as defensins, cathelicidins and lactoferrins directly or indirectly alter microbes or microbial growth. These proteins may not be considered as antibodies of the innate immune system. Hence, ficolins and collectins could be considered as specialized 'antibodies of the innate immune system' instead of 'ante-antibody' innate immune molecules. The discovery, structure, functions and future research directions of many of these soluble proteins and receptors such as Toll-like and NOD-like receptors are discussed in this special issue of Innate Immunity.


Assuntos
Anticorpos/imunologia , Colectinas/imunologia , Soroglobulinas/imunologia , Imunidade Adaptativa , Animais , Ativação do Complemento , Complemento C1q/metabolismo , Humanos , Imunidade Inata , Receptores Toll-Like/imunologia
11.
Influenza Other Respir Viruses ; 4(1): 1-5, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20021501

RESUMO

BACKGROUND: The 2009 novel A(H1N1) virus appears to be of swine origin. This strain causing the current outbreaks is a new virus that has not been seen previously either in humans or animals. We have previously reported that viruses causing pandemics or large outbreaks were able to grow at a temperature above the normal physiological range (temperature resistance, non-ts phenotype), were found to be inhibitor resistant and restricted in replication at suboptimal temperature (sensitivity to grow at low temperature, non-ca phenotype). In this study, we performed phenotypic analysis of novel A(H1N1) virus to evaluate its pandemic potential and its suitability for use in developing a live attenuated influenza vaccine. OBJECTIVES: The goal of this study is to identify phenotypic properties of novel A(H1N1) influenza virus. METHODS: A/California/07/2009 (H1N1) swine-origin influenza virus was studied in comparison with some influenza A viruses isolated in different years with respect to their ability to grow at non-permissive temperatures. We also analyzed its sensitivity to gamma-inhibitors of animal sera and its ability to agglutinate chicken, human and guinea pig erythrocytes. RESULTS: Swine-origin A/California/07/2009 (H1N1) virus was found to be non-ts and inhibitor resistant and was not able to grow at 25 degrees C (non-ca). We did not find any difference in the ability of the hemagglutinin of A/California/07/2009 (H1N1) virus to bind to erythrocytes of different origin. CONCLUSION: The novel swine-origin A(H1N1) virus displays a phenotype typical of the past pandemic and epidemic viruses. This finding suggests that this virus might be a good wild type parental prototype for live vaccine for potential use for controlling pandemic influenza.


Assuntos
Surtos de Doenças , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Adaptação Fisiológica , Animais , California/epidemiologia , Galinhas , Farmacorresistência Viral , Cobaias , Hemaglutinação por Vírus , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vacinas contra Influenza/imunologia , Testes de Neutralização , Infecções por Orthomyxoviridae/virologia , Soroglobulinas/imunologia , Suínos/virologia , Temperatura
12.
Pol J Vet Sci ; 9(4): 265-75, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17203746

RESUMO

Conglutinin, collectin-43 (CL-43) and collectin-46 (CL-46) are serum proteins characteristic for Bovidae. They belong to collectins--family of oligomeric proteins composed of trimeric subunits containing collagen-like sequences joined to C-type lectin domains. The genes encoding conglutinin, CL-43 and CL-46 are located on the bovine chromosome 28, and phylogenetic analysis indicates their common origin--from the lung surfactant protein D gene. Northern blot or immunocytochemical analysis confirm biosynthesis of bovine collectins mainly in the liver (conglutinin, CL-43) and in the thymus (CL-46). The level of conglutinin in the serum of dairy cows depends on many factors such as breeding, the season of the year, the stage of the reproductive cycle and infection. The collectins are involved in the innate immune defense. They bind to microbial surface carbohydrates inducing aggregation and, thereby, impeding infectivity. On the other hand the destruction of pathogens occurs due to stimulation of effector cells. CL-43 as well as conglutinin, binds to the collectin receptor (C1qR) localized on many types of cells identified as a surface variant of calreticulin. Conglutinin and CL-43 show antiviral activities towards influenza A virus and rotaviruses. Conglutinin also displays protective activity against bacterial infections.


Assuntos
Colectinas , Soroglobulinas , Animais , Bactérias/imunologia , Bovinos , Colectinas/sangue , Colectinas/química , Colectinas/genética , Colectinas/imunologia , Soroglobulinas/química , Soroglobulinas/genética , Soroglobulinas/imunologia , Vírus/imunologia
13.
Int Arch Allergy Immunol ; 138(4): 273-7, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16220003

RESUMO

BACKGROUND: Allergic cross-reactions are an issue of major concern because of implications for public health. The molecular basis of cross-allergy is the similarity of epitopes belonging to proteins of different organisms. Lupine is an emerging cause of food allergy, which has become a 'hot topic' because of recent large-scale introduction into processed foods and frequent cross-reactions with other members of the legume family. However, no lupine allergen has been characterized thus far. Prompted by a recently reported case of peanut-lupine cross-allergy, we wished to identify the possible cross-reactive allergen(s) between the two vegetal species. METHODS: We used computer-aided amino acid sequence comparison, a well-established technique for the study of protein homology, and followed the FAO/WHO guidelines for the identification of potential allergens. We also performed a three-dimensional modeling of the suspected cross-reactive proteins to compare their molecular surfaces. RESULTS: We found a highly significant sequence homology and molecular similarity between allergen Ara h 8 of peanut and pathogenesis-related protein PR-10 of white lupine. Another protein of lupine, the beta-conglutin precursor, was found to be significantly homologous to the Ara h 1 allergen of peanut. The molecular surfaces of Ara h 8 and PR-10 were remarkably similar. CONCLUSIONS: Our in silico data allow to predict the allergenicity of PR-10 and beta-conglutin precursor of white lupine according to FAO/WHO guidelines. Amino acid sequence homology also suggests that these proteins could be responsible, at least in part, for some of the allergic cross-reactions between peanut and lupine reported in the literature.


Assuntos
Antígenos de Plantas/imunologia , Arachis/imunologia , Lupinus/imunologia , Alérgenos , Sequência de Aminoácidos , Antígenos de Plantas/genética , Arachis/genética , Colectinas/química , Colectinas/genética , Colectinas/imunologia , Reações Cruzadas/imunologia , Glicoproteínas , Lupinus/genética , Proteínas de Membrana , Modelos Moleculares , Dados de Sequência Molecular , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Homologia de Sequência de Aminoácidos , Soroglobulinas/química , Soroglobulinas/genética , Soroglobulinas/imunologia
14.
Am J Pathol ; 164(6): 1967-77, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15161633

RESUMO

The involvement of proinflammatory cytokines interleukin (IL)-1 and tumor necrosis factor (TNF) in crescentic glomerulonephritis (GN) is well established. Recently the requirement of intrinsic renal cell participation via their production of TNF in crescentic GN was demonstrated. The current studies address the relative contributions of leukocyte and intrinsic renal cell-derived IL-1beta in the induction of TNF production and glomerular injury by studying bone marrow chimeric mice. Leukocyte-derived IL-1beta was critical in the development of crescentic renal injury because IL-1beta(-/-)-->WT (absent leukocyte IL-1beta) chimeric mice had significantly attenuated TNF expression and were protected from the development of crescentic GN. In contrast, WT-->IL-1beta(-/-) chimeric mice (intact leukocyte but absent renal IL-1beta) developed similar TNF expression and crescentic GN to wild-type mice. To determine the cellular target for IL-1 in this model, IL-RI chimeric mice were studied. IL-1RI(-/-)-->WT chimeric (absent leukocyte IL-1RI expression) mice showed no attenuation of crescentic GN, whereas in the absence of renal IL-1RI (WT-->IL-1RI(-/-) chimeras), glomerular TNF expression and the development of crescentic GN were significantly decreased. These studies demonstrate that leukocytes are the major cellular source of IL-1beta, and that IL-1beta acts principally via the IL-1RI on intrinsic renal cells to induce TNF expression and crescentic glomerular injury.


Assuntos
Transplante de Medula Óssea/imunologia , Glomerulonefrite/patologia , Interleucina-1/fisiologia , Rim/imunologia , Receptores de Interleucina-1/genética , Fator de Necrose Tumoral alfa/genética , Animais , Formação de Anticorpos , Modelos Animais de Doenças , Regulação da Expressão Gênica/imunologia , Glomerulonefrite/imunologia , Glomerulonefrite/fisiopatologia , Interleucina-1/deficiência , Interleucina-1/genética , Leucócitos/imunologia , Camundongos , Camundongos Knockout , Receptores de Interleucina-1/imunologia , Receptores Tipo I de Interleucina-1 , Soroglobulinas/imunologia , Ovinos , Quimeras de Transplante
15.
Q J Nucl Med Mol Imaging ; 48(4): 251-7, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15640788

RESUMO

The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antineoplásicos/imunologia , Reações Antígeno-Anticorpo/imunologia , Neoplasias/imunologia , Radioimunoterapia/métodos , Soroglobulinas/imunologia , Anticorpos Monoclonais/efeitos adversos , Humanos , Neoplasias/radioterapia , Radioimunoterapia/efeitos adversos
16.
Bull Exp Biol Med ; 133(2): 156-9, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12428284

RESUMO

A 36 kDa protein was isolated from the sera of patients with ovarian cancer and rabbit antisera to this protein were prepared. Precipitation test with these antisera detected an antigen with electrophoretic mobility corresponding to alpha-1-globulins and molecular weight of 36 kDa. Direct comparison of precipitating test systems showed that this antigen is not identical to the known carcinoembryonic, placental, and reactive proteins. Serum alpha-1-globulin was not detected in the sera of healthy humans, pregnant women, newborns, and in human adult and fetal visceral tissues at the level of precipitating test system sensitivity 1 mg/liter. It was detected in the sera of patients with ovarian cancer, in ovarian tumor (cancer) tissues, in the contents of ovarian tumor cavities, and in concentrated specimens of amniotic fluid. The antigen was not detected in ascitic fluid of patients with ovarian cancer, but it was present in 75% serum samples from these patients. The antigen was called serum oncoovarian alpha-1-globulin. SDS-PAAG electrophoresis showed that this antigen is an oligomer consisting of subunits (monomers) with molecular weight of 36 kDa. Under denaturing conditions in the presence of 2-mercaptoethanol these monomers dissociate into polypeptide chains with a molecular weight of 18 kDa. The protein is liable to oligomerization. Comparative characteristics of serum oncoovarian alpha-1-globulin and CA-125 antigen are presented.


Assuntos
Adenocarcinoma/sangue , Globulinas/química , Globulinas/metabolismo , Proteínas Oncogênicas/química , Proteínas Oncogênicas/metabolismo , Neoplasias Ovarianas/sangue , Soroglobulinas/química , Soroglobulinas/metabolismo , Adolescente , Animais , Biomarcadores Tumorais , Antígeno Ca-125/química , Antígeno Ca-125/metabolismo , Feminino , Globulinas/imunologia , Humanos , Masculino , Peso Molecular , Proteínas Oncogênicas/imunologia , Gravidez , Soroglobulinas/imunologia
17.
Immunobiology ; 205(4-5): 498-517, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12396011

RESUMO

Lung surfactant protein D (SP-D), conglutinin, CL-43 and CL-46 belong to a group of proteins designated collectins that, besides a common structure made of a collagen-like region and a C-type lectin domain, are important components of the innate immune defence. They all bind complex glycoconjugates on microorganisms thereby inhibiting infection, enhancing the clearance by phagocytes and modulating the immune response. In addition, SP-D inhibits the generation of radical oxygen species or the propagation of lipid peroxidation. Knock-out mice deficient in SP-D have a disturbed homeostasis of pulmonary surfactant and suffer from oxidative stress leading to pulmonary inflammation upon microbial challenge. Conglutinin, CL-43 and CL-46 have in contrast to the rest of the collectin family only been found in cattle. During the characterization of the genes encoding conglutinin, CL-43 and CL-46 we observed several features showing that the additional bovine collectins are diverted molecular descendants of an ancestral SP-D gene. Since structural similarity often associates with common functionality, some of SP-D's effector mechanisms may apply to conglutinin, CL-43 and CL-46--and vice versa. This review focus on the structural and functional relationship of this group of collectins.


Assuntos
Colectinas/genética , Colectinas/imunologia , Imunidade Inata/fisiologia , Proteínas Associadas a Surfactantes Pulmonares/genética , Proteínas Associadas a Surfactantes Pulmonares/imunologia , Soroglobulinas/genética , Soroglobulinas/imunologia , Animais , Bactérias/imunologia , Colectinas/química , Colectinas/metabolismo , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Pulmão/imunologia , Filogenia , Proteínas Associadas a Surfactantes Pulmonares/química , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Soroglobulinas/química , Soroglobulinas/metabolismo , Vírus/imunologia
18.
J Am Soc Nephrol ; 13(2): 350-358, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11805162

RESUMO

Proliferative glomerulonephritis in humans is characterized by the presence of leukocytes in glomeruli. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) can potentially stimulate or affect T cell, macrophage, and neutrophil function. To define the roles of GM-CSF and G-CSF in leukocyte-mediated glomerulonephritis, glomerular injury was studied in mice genetically deficient in either GM-CSF (GM-CSF -/- mice) or G-CSF (G-CSF -/- mice). Two models of glomerulonephritis were studied: neutrophil-mediated heterologous-phase anti-glomerular basement membrane (GBM) glomerulonephritis and T cell/macrophage-mediated crescentic autologous-phase anti-GBM glomerulonephritis. Both GM-CSF -/- and G-CSF -/- mice were protected from heterologous-phase anti-GBM glomerulonephritis compared with genetically normal (CSF WT) mice, with reduced proteinuria and glomerular neutrophil numbers. However, only GM-CSF -/- mice were protected from crescentic glomerular injury in the autologous phase, whereas G-CSF -/- mice were not protected and in fact had increased numbers of T cells in glomeruli. Humoral responses to the nephritogenic antigen were unaltered by deficiency of either GM-CSF or G-CSF, but glomerular T cell and macrophage numbers, as well as dermal delayed-type hypersensitivity to the nephritogenic antigen, were reduced in GM-CSF -/- mice. These studies demonstrate that endogenous GM-CSF plays a role in experimental glomerulonephritis in both the autologous and heterologous phases of injury.


Assuntos
Glomerulonefrite Membranoproliferativa/imunologia , Fator Estimulador de Colônias de Granulócitos/fisiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Neutrófilos/imunologia , Animais , Glomerulonefrite Membranoproliferativa/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/deficiência , Fator Estimulador de Colônias de Granulócitos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/deficiência , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Cavalos/sangue , Camundongos , Camundongos Endogâmicos , Camundongos Knockout/genética , Soroglobulinas/imunologia , Ovinos/sangue
19.
Rev. cuba. pediatr ; 71(3): 140-5, 1999. graf
Artigo em Espanhol | LILACS | ID: lil-254785

RESUMO

Para valorar la relación entre la enfermedad diarreica prolongada, el parasitismo intestinal y las alteraciones del sistema inmune se realizó un estudio a 325 niños, entre 8 meses y 6 años de edad, de la Consulta de Inmunología, entre enero de 1993 y junio de 1997; a éstos se les efectuó cuantificación de inmunoglobulinas séricas (IgG, IgA IgM) (n:157), la prueba cutánea de hipersensibilidad retardada con toxoide tetánico (n:60) y se midió el área tímica por ultrasonografía (n:108). De los pacientes con niveles bajos de inmunoglobulinas, el 77 porciento presentaba IgA deficiente. La prueba del toxoide tetánico demostró que el 85 porciento de los enfermos estudiados presentaban un déficit de inmunidad celular funcional y el 75 porciento del total de pacientes tenía área del timo disminuida y de ellos 42 (39 porciento) mostraban atrofia severa de este órgano. Esto nos permite concluir que el déficit de inmunidad celular en estos casos es predominante, lo que permitió el empleo de una inmunoterapia adecuada


Assuntos
Diarreia Infantil , Imunoterapia , Soroglobulinas/imunologia , Toxoide Tetânico/uso terapêutico
20.
Rev. cuba. pediatr ; 71(3): 140-5, 1999. graf
Artigo em Espanhol | CUMED | ID: cum-16614

RESUMO

Para valorar la relación entre la enfermedad diarreica prolongada, el parasitismo intestinal y las alteraciones del sistema inmune se realizó un estudio a 325 niños, entre 8 meses y 6 años de edad, de la Consulta de Inmunología, entre enero de 1993 y junio de 1997; a éstos se les efectuó cuantificación de inmunoglobulinas séricas (IgG, IgA IgM) (n:157), la prueba cutánea de hipersensibilidad retardada con toxoide tetánico (n:60) y se midió el área tímica por ultrasonografía (n:108). De los pacientes con niveles bajos de inmunoglobulinas, el 77 porciento presentaba IgA deficiente. La prueba del toxoide tetánico demostró que el 85 porciento de los enfermos estudiados presentaban un déficit de inmunidad celular funcional y el 75 porciento del total de pacientes tenía área del timo disminuida y de ellos 42 (39 porciento) mostraban atrofia severa de este órgano. Esto nos permite concluir que el déficit de inmunidad celular en estos casos es predominante, lo que permitió el empleo de una inmunoterapia adecuada (AU)


Assuntos
Soroglobulinas/imunologia , Toxoide Tetânico/uso terapêutico , Imunoterapia , Diarreia Infantil
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