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1.
Nano Lett ; 19(9): 5844-5852, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31424944

RESUMO

The majority of developed and approved anticancer nanomedicines have been designed to exploit the dogma of the enhanced permeability and retention (EPR) effect, which is based on the leakiness of the tumor's blood vessels accompanied by impeded lymphatic drainage. However, the EPR effect has been under scrutiny recently because of its variable manifestation across tumor types and animal species and its poor translation to human cancer therapy. To facilitate the EPR effect, systemically injected NPs should overcome the obstacle of rapid recognition and elimination by the mononuclear phagocyte system (MPS). We hypothesized that circulating monocytes, major cells of the MPS that infiltrate the tumor, may serve as an alternative method for achieving increased tumor accumulation of NPs, independent of the EPR effect. We describe here the accumulation of liposomal quantum dots (LipQDs) designed for active delivery via monocytes, in comparison to LipQDs designed for passive delivery (via the EPR effect), following IV administration in a mammary carcinoma model. Hydrophilic QDs were synthesized and entrapped in functionalized liposomes, conferring passive ("stealth" NPs; PEGylated, neutral charge) and active (monocyte-mediated delivery; positively charged) properties by differing in their lipid composition, membrane PEGylation, and charge (positively, negatively, and neutrally charged). The various physicochemical parameters affecting the entrapment yield and optical stability were examined in vitro and in vivo. Biodistribution in the blood, various organs, and in the tumor was determined by the fluorescence intensity and Cd analyses. Following the treatment of animals (intact and mammary-carcinoma-bearing mice) with disparate formulations of LipQDs (differing by their lipid composition, neutrally and positively charged surfaces, and hydrophilic membrane), we demonstrate comparable tumor uptake of QDs delivered by the passive and the active routes (mainly by Ly-6Chi monocytes). Our findings suggest that entrapping QDs in nanosized liposomal formulations, prepared by a new facile method, imparts superior structural and optical stability and a suitable biodistribution profile leading to increased tumor uptake of fluorescently stable QDs.


Assuntos
Lipossomos/farmacologia , Neoplasias Mamárias Animais/tratamento farmacológico , Sistema Fagocitário Mononuclear/química , Pontos Quânticos/química , Animais , Vasos Sanguíneos/efeitos dos fármacos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Lipídeos/química , Lipídeos/farmacologia , Lipossomos/química , Neoplasias Mamárias Animais/patologia , Camundongos , Nanomedicina , Células Neoplásicas Circulantes , Permeabilidade/efeitos dos fármacos
2.
ACS Nano ; 11(10): 10539-10548, 2017 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-28953351

RESUMO

The clearance of nanoparticles (NPs) by mononuclear phagocyte system (MPS) from blood leads to high liver and spleen uptake and negatively impacts their tumor delivery efficiency. Here we systematically evaluated the in vitro and in vivo nanobio interactions of a two-dimensional (2D) model, gold (Au) nanorings, which were compared with Au nanospheres and Au nanoplates of similar size. Among different shapes, Au nanorings achieved the lowest MPS uptake and highest tumor accumulation. Among different sizes, 50 nm Au nanorings showed the highest tumor delivery efficiency. In addition, we demonstrated the potential use of Au naonrings in photoacoustic imaging and photothermal therapy. Thus, engineering the shape, surface area, and size of Au nanostructures is important in controlling NP-MPS interactions and improving the tumor uptake efficiency.


Assuntos
Antineoplásicos/farmacologia , Ouro/farmacologia , Sistema Fagocitário Mononuclear/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fototerapia , Animais , Antineoplásicos/química , Diagnóstico por Imagem , Ouro/química , Macrófagos/efeitos dos fármacos , Camundongos , Sistema Fagocitário Mononuclear/imunologia , Neoplasias/diagnóstico , Tamanho da Partícula , Tomografia por Emissão de Pósitrons , Células RAW 264.7 , Propriedades de Superfície , Distribuição Tecidual
3.
Actas Dermosifiliogr ; 100(1): 46-52, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19268111

RESUMO

INTRODUCTION: Oral lichen planus (OLP) is a relatively common inflammatory disease with a wide range of clinical forms. Its pathogenesis has not been fully elucidated although it is known to be mediated by lymphocytes with the participation of cytokines and other inflammatory cells, including type I and type II dermal dendrocytes (DD) (factor XIIIa+ DD and CD34+ DD, respectively). OBJECTIVES: To describe the presence and tissue distribution of these cells, through immunohistochemistry, in 23 specimens from patients with clinical and histopathological criteria of OLP. RESULTS: Factor XIIIa+ DD were mainly located in the superficial dermis (p < 0.0001) as opposed to the deep submucosa. These cells were abundant throughout the dermal-epidermal junction and closely related to lymphocyte infiltration. Moreover, factor XIIIa+ DD were also found in the epithelium and deep dermis. CD34+ DD were distributed mostly to the deep dermis directly below the lymphocyte infiltrate with few cells in the subepithelial region. CONCLUSIONS: DD were present in OLP, with distinct tissue distributions. Factor XIIIa+ DD were predominant in the superficial dermis while CD34+ DD could be found mostly in the deep dermis. These findings suggest that DD, and those positive for factor XIIIa+ in particular in view of their ability to express intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor alpha (TNF-alpha), may play an important role in pathogenesis of OLP.


Assuntos
Líquen Plano Bucal/patologia , Sistema Fagocitário Mononuclear/patologia , Antígenos CD34/análise , Antígenos de Diferenciação/análise , Biópsia , Células da Medula Óssea/citologia , Linhagem da Célula , Fator XIIIa/análise , Antígenos HLA-DR/análise , Humanos , Líquen Plano Bucal/imunologia , Sistema Fagocitário Mononuclear/química , Sistema Fagocitário Mononuclear/imunologia , Estudos Retrospectivos
4.
Actas dermo-sifiliogr. (Ed. impr.) ; 100(1): 46-52, ene. 2009. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-128209

RESUMO

Introducción: El liquen plano oral (LPO) es una enfermedad inflamatoria relativamente frecuente que se presenta con un amplio abanico de formas clínicas. Todavía no se ha determinado completamente su patogenia, aunque se sabe que los linfocitos actúan de mediadores con la participación de citoquinas y otras células inflamatorias, entre ellas los dendrocitos dérmicos (DD) tipo I y tipo II (DD positivos para el factor XIIIA y CD34, respectivamente).Objetivos. Describir la presencia y distribución de estas células en el tejido, mediante técnicas inmunohistoquímicas, en 23 muestras procedentes de pacientes que reunían los criterios clínicos e histopatológicos de LPO. Resultados: Los DD factor XIII+ estaban localizados principalmente en la dermis superficial (p < 0,0001) y no en la submucosa profunda. Dichas células se encontraban en abundancia en toda la unión dermoepidérmica y se relacionaban estrechamente con la infiltración linfocitaria. Los DD factor XIIIa+ se encontraban además en el epitelio y la dermis profunda. En cambio, los DD CD34+ se distribuyeron principalmente en la dermis profunda, directamente por debajo del infiltrado linfocitario, con pocas células en la zona subepitelial. Conclusiones: Los DD estaban presentes en el LPO, con diferentes distribuciones en los tejidos. Así, los DD factor XIIIa+ predominaban en la dermis superficial, mientras que los DD CD34+ se encontraban principalmente en la dermis profunda. Esto apunta a que los DD, y sobre todo los DD factor XIIIa+ debido a su capacidad para expresar moléculas de adhesión intercelulares-1 (ICAM-1) y el factor de necrosis tumoral alfa (TNF-α), pueden desempeñar una función destacada en la patogénesis del LPO (AU)


Introduction: Oral lichen planus (OLP) is a relatively common inflammatory disease with a wide range of clinical forms. Its pathogenesis has not been fully elucidated although it is known to be mediated by lymphocytes with the participation of cytokines and other inflammatory cells, including type I and type II dermal dendrocytes (DD) (factor xiIIa+ DD and CD34+ DD, respectively). Objectives: To describe the presence and tissue distribution of these cells, through immunohistochemistry, in 23 specimens from patients with clinical and histopathological criteria of OLP. Results: Factor xiIIa+ DD were mainly located in the superficial dermis (p < 0.0001) as opposed to the deep submucosa. These cells were abundant throughout the dermal-epidermal junction and closely related to lymphocyte infiltration. Moreover, factor xiIIa+ DD were also found in the epithelium and deep dermis. CD34+ DD were distributed mostly to the deep dermis directly below the lymphocyte infiltrate with few cells in the subepithelial region. Conclusions: DD were present in OLP, with distinct tissue distributions. Factor xiIIa+ DD were predominant in the superficial dermis while CD34+ DD could be found mostly in the deep dermis. These findings suggest that DD, and those positive for factor xiIIa+ in particular in view of their ability to express intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor α (TNF-α), may play an important role in pathogenesis of OLP (AU)


Assuntos
Humanos , Antígenos CD34/análise , Antígenos de Diferenciação/análise , Células da Medula Óssea/citologia , Fator XIIIa/análise , Antígenos HLA-DR/análise , Líquen Plano Bucal/imunologia , Líquen Plano Bucal/patologia , Sistema Fagocitário Mononuclear/patologia , Biópsia , Linhagem da Célula , Sistema Fagocitário Mononuclear/química , Sistema Fagocitário Mononuclear/imunologia , Estudos Retrospectivos
5.
J Infect Dis ; 195(12): 1745-53, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17492589

RESUMO

Several lines of evidence have suggested that iron is critical for Mycobacterium tuberculosis growth in macrophages. Macrophage iron loading in patients with African iron overload increases the risk of tuberculosis (TB) and may worsen TB outcome. Likewise, macrophage iron loading may contribute to an increased predisposition toward TB in HIV infection. Human genetic disorders or variations may increase the risk of TB or worsen its outcome through macrophage iron loading, including the haptoglobin 2-2 phenotype, NRAMP1 polymorphisms (at least in Africans and Asians), and possibly ferroportin 1 mutations, but not HFE hemochromatosis. Thus, the host's iron status may be an important yet underevaluated factor in TB prevention and therapy and in TB vaccine design.


Assuntos
Sobrecarga de Ferro/complicações , Ferro/metabolismo , Macrófagos/metabolismo , Mycobacterium tuberculosis/crescimento & desenvolvimento , Tuberculose/etiologia , Antituberculosos/farmacologia , Proteínas de Transporte de Cátions/genética , Citocinas/metabolismo , Haptoglobinas/genética , Humanos , Sobrecarga de Ferro/genética , Macrófagos/química , Macrófagos/microbiologia , Sistema Fagocitário Mononuclear/química , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/imunologia , Tuberculose/tratamento farmacológico , Tuberculose/genética , Tuberculose/metabolismo , Vacinas contra a Tuberculose/normas
6.
Kidney Int Suppl ; (101): S4-8, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16830699

RESUMO

Routine monitoring of body iron stores is an essential component of overall management for the patient on hemodialysis. Adequate iron levels are important for the prevention and treatment of iron-deficiency anemia, which is associated with reduced physical functioning, cardiovascular disease, and poor quality of life. Hemodialysis patients are at especially high risk for iron-deficiency anemia, owing to continuous blood losses and supraphysiologic levels of erythropoiesis driven by recombinant human erythropoietin therapy. Unfortunately, the accurate determination of iron status in these patients can be a challenging task, which is made more difficult by inflammation, infections, and the large number of comorbid conditions that can affect commonly used indices of body iron stores. Despite their limitations, transferrin saturation (TSAT) and serum ferritin remain the cornerstones of iron status assessment. Because these values can be altered by a number of non-iron-related factors, it is necessary to go beyond these measures and draw upon additional sources of information to determine the patient's iron status. Other important factors to consider when assessing the need for iron therapy include evidence of underlying inflammatory processes that may block iron mobilization and distort the standard iron indices, the results of alternative iron indices, and the patient's recent history of iron administration. Frequently, the response to a gram of intravenous (i.v.) iron is a safe and effective way to determine the role of iron deficiency in the anemia of the problematic patient. The chronic inflammatory state associated with malnutrition and clinical or subclinical infections substantially increases the risk of misdiagnosing the patient with iron overload and may place the patient at risk of iron deficiency owing to inappropriate withdrawal of i.v. iron therapy. To avoid the risks of withholding iron therapy, the nephrologist must keep this relationship in mind whenever serum ferritin testing suggests replete iron stores, whereas TSAT testing suggests insufficient iron availability.


Assuntos
Anemia Ferropriva/diagnóstico , Anemia Ferropriva/etiologia , Ferritinas/sangue , Hemossiderose/sangue , Transferrina/análise , Medula Óssea/química , Eritroblastos/química , Eritropoese/fisiologia , Ferritinas/análise , Hemoglobinas/análise , Hemossiderose/fisiopatologia , Humanos , Inflamação/sangue , Ferro/metabolismo , Ferro/uso terapêutico , Fígado/química , Sistema Fagocitário Mononuclear/química , Desnutrição Proteico-Calórica/sangue , Receptores da Transferrina/análise , Diálise Renal/efeitos adversos , Reticulócitos/química , Sensibilidade e Especificidade
7.
J Clin Pathol ; 57(3): 300-2, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14990604

RESUMO

BACKGROUND: Immunocytochemical accumulation of prion protein (PrP) in lymphoid tissues is a feature of variant Creutzfeldt-Jakob disease (vCJD) that has been used both to aid in the diagnosis of patients and as a basis of large scale screening studies to assess the prevalence of preclinical disease in the UK. However, the specificity of this approach is unknown. AIM: To assess the specificity of lymphoreticular accumulation of PrP for vCJD by examining a range of human diseases. METHODS: Paraffin wax embedded lymphoreticular tissues from patients with several reactive conditions (58 cases), tumours (27 cases), vCJD (54 cases), and other human prion diseases (56 cases) were assessed. PrP accumulation was assessed by immunocytochemistry using two different monoclonal anti-PrP antibodies and a sensitive detection system. RESULTS: All cases of vCJD showed widespread lymphoreticular accumulation of PrP; however, this was not seen in the other conditions examined. CONCLUSION: Lymphoreticular accumulation of PrP, as assessed by immunocytochemistry, appears to be a highly specific feature of vCJD.


Assuntos
Síndrome de Creutzfeldt-Jakob/metabolismo , Tecido Linfoide/química , Sistema Fagocitário Mononuclear/química , Príons/análise , Western Blotting , Humanos , Imuno-Histoquímica/métodos , Inflamação/metabolismo , Neoplasias/química , Proteínas PrPSc/análise , Doenças Priônicas/metabolismo , Sensibilidade e Especificidade
8.
Br Med Bull ; 66: 267-79, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14522864

RESUMO

Prion diseases are usually diagnosed clinically and confirmed by post-mortem histopathological examination of brain tissue. The only reliable molecular marker for prion diseases is PrP(Sc), the pathological conformer of the prion protein that accumulates in the central nervous system and, to a lesser extent, in lymphoreticular tissues. For BSE, several commercial diagnostic kits based on the post-mortem immunochemical detection of PrP(Sc) in brain tissue are now available. These rapid screening tests have been used in active surveillance of BSE and have greatly improved the detection of infected cattle before their entry into the human food chain. At present, no diagnostic test exists for the detection of prion diseases in live animals or humans. New diagnostic techniques aimed at increasing sensitivity and specificity of PrP(Sc) detection in body fluids and at identifying novel surrogate markers are under development. In this report, we review the classical diagnostic methods as well as present and future tools for the diagnosis of prion diseases.


Assuntos
Proteínas PrPSc/análise , Doenças Priônicas/diagnóstico , Animais , Autopsia , Biomarcadores/análise , Western Blotting , Encéfalo/patologia , Química Encefálica , Bovinos , Encefalopatia Espongiforme Bovina/diagnóstico , Endopeptidases/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imuno-Histoquímica , Tecido Linfoide/química , Sistema Fagocitário Mononuclear/química , Proteína PrP 27-30/genética , Proteínas PrPC/análise , Proteínas PrPC/metabolismo , Proteínas PrPSc/genética , Proteínas PrPSc/metabolismo , Valor Preditivo dos Testes , Doenças Priônicas/patologia , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Zoonoses
10.
Acta Anat (Basel) ; 149(3): 209-14, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7976171

RESUMO

The morphology of reticular cells of the sheathed arteries, in the red pulp of pig spleen, was studied by using transmission electron microscopy; and their histochemical reactivity with periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP). The phagocytic ability was evaluated by injecting colloidal carbon into the splenic artery. Reticular cells of the sheathed arteries were classified as type I and type II cells. Type I cells have a nucleus with scanty chromatin, and the cytoplasm reacts positively to PA-TCH-SP. The PA-TCH-SP-positive granules are considered to be subunits of beta-glycogen particles based on their morphological features. Type II cells have a nucleus with abundant chromatin and are not stained by PA-TCH-SP. Both types of reticular cells are connected with reticular fibers. Results of the colloidal carbon injection showed that type I reticular cells did not ingest carbon particles during the time frame of the experiment, whereas type II reticular cells are phagocytic and ingested carbon.


Assuntos
Capilares/citologia , Sistema Fagocitário Mononuclear/citologia , Baço/irrigação sanguínea , Animais , Capilares/química , Capilares/ultraestrutura , Carbono , Coloides , Endotélio Vascular/ultraestrutura , Glicogênio/análise , Injeções Intra-Arteriais , Microscopia Eletrônica , Sistema Fagocitário Mononuclear/química , Sistema Fagocitário Mononuclear/ultraestrutura , Fagocitose , Baço/ultraestrutura , Suínos
11.
J Leukoc Biol ; 52(1): 27-33, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1640172

RESUMO

We have examined the tissue distribution of 10-kd inflammatory protein (IP-10) mRNA expression in C57Bl/6 mice injected intravenously (i.v.) with various inflammatory stimuli. IP-10 mRNA was strongly induced by interferon-gamma (IFN-gamma) in liver and kidney but only poorly in skin, heart, and lung. IFN-gamma had nearly equivalent access to these tissues as indicated by the distribution of radiolabeled recombinant IFN-gamma 1 h after injection. The time course of IP-10 mRNA appearance was rapid and transient in both liver and kidney; maximal expression in the liver (2 h) preceded that in the kidney (3 h) and declined rapidly thereafter in both tissues. Expression of IP-10 mRNA in the liver and kidney was highly sensitive to IFN-gamma treatment; nearly maximal stimulation occurred with injection of 500 U of IFN-gamma per mouse. Comparable stimulation of IP-10 mRNA expression in splenic macrophages required 10,000 U of IFN-gamma administered i.v., indicating that liver and kidney responses are 10- to 20-fold more sensitive. IP-10 mRNA expression in both tissues was not restricted to stimulation by IFN-gamma but was also seen with injection of lipopolysaccharide (LPS) (25 micrograms/mouse) or IFN-beta (100,000 U/mouse). Two other members of the IP-10 gene family, KC (gro) and JE (MCP-1), were expressed at lower levels under similar treatment conditions. Analysis of IP-10 mRNA distribution in the liver and kidney by in situ hybridization indicated that expression in both tissues was most prominent in the reticuloendothelial cell system, particularly in the endothelial lining of the microvascular circulation. Although the function of the IP-10 gene product has not been defined, these results suggest that it may play an important role in the response of both the liver and kidney to systemic inflammation.


Assuntos
Quimiocinas CXC , Citocinas/genética , RNA Mensageiro/análise , Animais , Quimiocina CXCL10 , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Inflamação/diagnóstico , Interferon gama/farmacologia , Rim/química , Rim/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Fígado/química , Fígado/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Sistema Fagocitário Mononuclear/química , Hibridização de Ácido Nucleico , Especificidade de Órgãos
12.
Br J Haematol ; 81(1): 118-24, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1381604

RESUMO

Human H-ferritin homopolymer was denatured in sodium dodecyl sulphate and injected in mice to obtain antibodies for dissociated H-subunit. The antisera and Moabs obtained were specific for the denatured H-chain with no cross-reactivity with assembled ferritins in immunoblotting experiments. In contrast the Moabs for native recombinant H-ferritin are specific for the assembled ferritin molecules with weak cross-reactivity with the denatured H-subunits. The epitope recognized by one of the anti-denatured H-chain Moabs was mapped on the C-terminal helix of ferritin. The antibodies were used to study H-ferritin conformation in cells. In immunocytochemistry experiments the antibodies for denatured H-ferritin stained HeLa and K562 cells weakly, with a different intensity and pattern to those obtained with anti-native H-ferritin antibody. In human bone marrow smears the anti-denatured ferritin antibodies stained only reticuloendothelial cells, and did not recognize the H-ferritin rich immature erythroblasts. It is concluded that assembled and denatured H-ferritins are immunogenically distinct, and that erythroid and reticuloendothelial cells within the bone marrow contain H-ferritin in different conformations.


Assuntos
Anticorpos Monoclonais , Células da Medula Óssea , Ferritinas/imunologia , Sistema Fagocitário Mononuclear/química , Sistema Fagocitário Mononuclear/citologia , Western Blotting , Medula Óssea/química , Medula Óssea/imunologia , Eletroforese em Gel de Poliacrilamida , Células Precursoras Eritroides/química , Células Precursoras Eritroides/citologia , Células Precursoras Eritroides/imunologia , Imunofluorescência , Células HeLa , Humanos , Imuno-Histoquímica , Ferro/metabolismo , Desnaturação Proteica , Coloração e Rotulagem
13.
Cell Tissue Res ; 266(2): 223-9, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1764725

RESUMO

Monoclonal antibodies against cellular components of reticular meshworks were produced by immunizing rats with heterogeneous stromal-cell population of mouse spleen. Immunohistochemical screening selected two antibodies, WP-1 and RPSC-2. WP-1 proved to immunostain the meshwork of the B area densely, leaving the marginal zone unstained; it also reacted sparsely with the meshwork of the T-cell region. In contrast, RPSC-2 selectively immunostained the meshwork of the T region. Immuno-electron microscopy clearly visualized, for both antibodies, reaction products being deposited along the cytomembrane of the fibroblastic reticulum cells, along their abundant cytoplasmic processes that were densely intertwined with lymphocytes. Double immunostaining with RPSC-2 followed by WP-1 clearly divided the white pulp into the T and the B domains. The meshwork in the T-cell region proved to be immunostainable with both WP-1 and RPSC-2. Thus, the fibroblastic reticulum cells of the T- and the B-cell areas, while indistinguishable by routine microscopy, are at least partially heterogeneous.


Assuntos
Linfócitos B/química , Sistema Fagocitário Mononuclear/citologia , Baço/citologia , Linfócitos T/química , Animais , Anticorpos Monoclonais , Diferenciação Celular , Células Dendríticas/química , Feminino , Fibroblastos/química , Imuno-Histoquímica , Macrófagos/química , Camundongos , Camundongos Endogâmicos , Microscopia Imunoeletrônica , Sistema Fagocitário Mononuclear/química , Ratos , Ratos Endogâmicos , Baço/química
14.
Br J Haematol ; 76(3): 427-32, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2261353

RESUMO

We have used the monoclonal antibodies 2A4 (specific for the H subunit of human ferritin) and LO3 (specific for the L subunit) for immunocytochemical detection of ferritin in bone marrow and peripheral blood cells from normal subjects and patients with various haematological disorders. Formalin-fixed slides were stained by the immunoalkaline phosphatase procedure (APAAP). In normal subjects, ferritin could be found only in bone marrow smears and appeared to be largely confined to erythroid precursors and reticuloendothelial cells. The more immature erythroid precursors contained higher concentrations of cellular ferritin. Although evaluation could be only semiquantitative, erythroblast ferritin appeared to be more reactive with the monoclonal 2A4 (15 +/- 7% positive erythroblasts) than with the monoclonal LO3 (6 +/- 5% positive erythroblasts), indicating that H-type ferritin was predominant, particularly in proerythroblasts and basophilic erythroblasts. By contrast, the ferritin present in reticuloendothelial cells appeared to be predominantly of L-type. Patients with iron deficiency showed low levels of positive erythroblast, whereas the reverse was true in patients with transfusional iron overload. Intense positivity for reticuloendothelial cell ferritin was found in patients with anaemia of chronic disease. In myelodysplastic syndromes and acute myeloid leukaemia (AML), ferritin positivity was generally very strong at any stage of erythroblast development, particularly with the monoclonal antibody 2A4. Perls-positive perinuclear granules of ring sideroblasts were not stained, confirming that mitochondrial iron deposition is not in the form of ferritin. In AML and myelodysplastic syndromes with excess of blasts, ferritin could be detected also in immature myeloid cells. These data indicate that: (a) in normal conditions ferritin is mainly expressed in red cell precursors and reticuloendothelial cells, and this is in keeping with the peculiar role of these cells in iron metabolism; (b) abnormal cell ferritin contents can be observed in both iron overload and malignancy.


Assuntos
Anticorpos Monoclonais , Medula Óssea/química , Ferritinas/análise , Eritroblastos/química , Células Precursoras Eritroides/química , Feminino , Ferritinas/sangue , Doenças Hematológicas/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Sistema Fagocitário Mononuclear/química
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