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1.
Int J Mol Sci ; 25(11)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38892362

RESUMEN

During the first era of humanity, the conditions of life, including hunting, fighting, obtaining food, and diseases, were associated with frequent hemorrhages, anemia, and infections, which led to death or untreatable conditions [...].


Asunto(s)
Eritrocitos , Humanos , Eritrocitos/metabolismo , Animales , Anemia/genética
2.
Int J Mol Sci ; 24(11)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37298597

RESUMEN

Inflammation has been described for two millennia, but cellular aspects and the paradigm involving different mediators have been identified in the recent century. Two main groups of molecules, the prostaglandins (PG) and the cytokines, have been discovered and play a major role in inflammatory processes. The activation of prostaglandins PGE2, PGD2 and PGI2 results in prominent symptoms during cardiovascular and rheumatoid diseases. The balance between pro- and anti-inflammatory compounds is nowadays a challenge for more targeted therapeutic approaches. The first cytokine was described more than a century ago and is now a part of different families of cytokines (38 interleukins), including the IL-1 and IL-6 families and TNF and TGFß families. Cytokines can perform a dual role, being growth promotors or inhibitors and having pro- and anti-inflammatory properties. The complex interactions between cytokines, vascular cells and immune cells are responsible for dramatic conditions and lead to the concept of cytokine storm observed during sepsis, multi-organ failure and, recently, in some cases of COVID-19 infection. Cytokines such as interferon and hematopoietic growth factor have been used as therapy. Alternatively, the inhibition of cytokine functions has been largely developed using anti-interleukin or anti-TNF monoclonal antibodies in the treatment of sepsis or chronic inflammation.


Asunto(s)
COVID-19 , Prostaglandinas , Humanos , Prostaglandinas/metabolismo , Citocinas/metabolismo , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inflamación/tratamiento farmacológico , Interleucinas/uso terapéutico , Prostaglandinas Sintéticas , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
3.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-36361758

RESUMEN

Cancer is a predominant cause of mortality all over the world. Lung, prostate, and colorectal cancer are the more frequent in men while breast and colorectal have a high incidence in women. Major progress aside, some cancers are still frequent and one major issue is improvements in detection methods. Imaging techniques have a major role, but inflammatory, tumoral markers and calculated scores may contribute to the assessment of prognosis. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and carcinoembryonic antigen cell adhesion molecule (CEACAM) have been used for decades and do not have a clear use for diagnosis or prognosis yet. The CEACAM family includes 12 human members, and some of them have a cluster differentiation (CD). CD66 may be an interesting indicator of disease severity. Beside interleukin-6 (IL-6), the high level of which is observed in patients with a high mortality rate, other cytokines IL-17A, IL-22, and transforming growth factor -ß (TGF-ß) are expressed at the tumor level. The detection of circulating tumor cells has been improved but is still of undetermined value. Circulating tumor DNA (ctDNA) was recently studied in CRC stage II patients and may be helpful for chemotherapy management.


Asunto(s)
ADN Tumoral Circulante , Neoplasias Colorrectales , Células Neoplásicas Circulantes , Masculino , Humanos , Femenino , Neoplasias Colorrectales/patología , Antígeno Carcinoembrionario , Biomarcadores de Tumor/genética , Células Neoplásicas Circulantes/metabolismo , Proteína C-Reactiva
4.
Int J Mol Sci ; 23(7)2022 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-35409010

RESUMEN

Vascular permeability is a selective mechanism that maintains the exchange between vessels, tissues, and organs. The regulation was mostly studied during the nineteenth century by physiologists who defined physical laws and equations, taking blood, tissue interstitial, and oncotic pressure into account. During the last decades, a better knowledge of vascular cell functions and blood-vessel interactions opens a new area of vascular biology. Endothelial cell receptors vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule (ICAM), vascular endothelial growth factor receptor (VEGFR-2), receptor for advanced glycation end products (RAGE), and mediators were identified and their role in homeostasis and pathological situations was described. The molecular differences of endothelial cell junctions (tight, gap, and adherens junctions) and their role in vascular permeability were characterized in different organs. The main mediators of vasomotricity and permeability, such as prostaglandins, nitric oxide (NO), prostacyclin, vascular growth factor (VEGF), and cytokines, have been demonstrated to possess major functions in steady state and pathological situations. Leukocytes were shown to adhere to endothelium and migrate during inflammatory situations and infectious diseases. Increased vascular permeability is linked to endothelium integrity. Glycocalyx, when intact, may limit cancer cell metastasis. Biological modifications of blood and tissue constituents occurring in diabetes mellitus were responsible for increased permeability and, consequently, ocular and renal complications. Vascular pressure and fluidity are major determinants of pulmonary and cerebral edema. Beside the treatment of the infectious disease, of the blood circulation dysfunction and inflammatory condition, drugs (cyclooxygenase inhibitors) and specific antibodies anti-cytokine (anti-VEGF) have been demonstrated to reduce the severity and the mortality in diseases that exhibited enhanced vascular permeability.


Asunto(s)
Permeabilidad Capilar , Factor A de Crecimiento Endotelial Vascular , Permeabilidad Capilar/fisiología , Moléculas de Adhesión Celular/metabolismo , Endotelio Vascular/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
5.
Int J Mol Sci ; 22(12)2021 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-34199319

RESUMEN

Inflammation is an old concept that has started to be considered as an important factor in infection and chronic diseases. The role of leukocytes, the plasmatic components, then of the mediators such as prostaglandins, cytokines, and, in recent decades, of the endothelium has completed the concept of the inflammation process. The function of the endothelium appeared to be crucial as a regulator or the initiator of the inflammatory process. Culture of human endothelial cells and experimental systems made it possible to define the molecular basis of inflammation in vascular diseases, in diabetes mellitus, atherosclerosis, vasculitis and thromboembolic complications. Advanced glycation end product receptor (RAGE), present on endothelial cells (ECs) and monocytes, participates in the activation of these cells in inflammatory conditions. Inflammasome is a cytosolic multiprotein that controls the response to diverse microorganisms. It is positively regulated by stimulator of interferon response CGAMP interactor-1 (STING1). Angiogenesis and thrombotic events are dysregulated during inflammation. ECs appear to be a protector, but also a possible initiator of thrombosis.


Asunto(s)
Aterosclerosis/patología , Endotelio Vascular/metabolismo , Trombosis/patología , Aterosclerosis/metabolismo , Endotelio Vascular/citología , Humanos , Inflamasomas/metabolismo , Proteínas de la Membrana/metabolismo , Neovascularización Fisiológica , Óxido Nítrico/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Trombosis/metabolismo
6.
Int J Mol Sci ; 21(15)2020 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-32727002

RESUMEN

In physiology and pathophysiology the molecules involved in blood cell-blood cell and blood cell-endothelium interactions have been identified. Platelet aggregation and adhesion to the walls belonging to vessels involve glycoproteins (GP), GP llb and GP llla and the GP Ib-IX-V complex. Red blood cells (RBCs) in normal situations have little interaction with the endothelium. Abnormal adhesion of RBCs was first observed in sickle cell anemia involving vascular cell adhesion molecule (VCAM)-1, α4ß1, Lu/BCAM, and intercellular adhesion molecule (ICAM)-4. More recently RBC adhesion was found to be increased in retinal-vein occlusion (RVO) and in polycythemia vera (PV). The molecules which participate in this process are phosphatidylserine and annexin V in RVO, and phosphorylated Lu/BCAM and α5 laminin chain in PV. The additional adhesion in diabetes mellitus occurs due to the glycated RBC band 3 and the advanced glycation end-product receptors. The multiligand receptor binds advanced glycation end products (AGEs) or S100 calgranulins, or ß-amyloid peptide. This receptor for advanced glycation end products is known as RAGE. The binding to RAGE-activated endothelial cells leads to an inflammatory reaction and a prothrombotic state via NADPH activation and altered gene expression. RAGE blockade is a potential target for drugs preventing the deleterious consequences of RAGE activation.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Células Endoteliales/metabolismo , Eritrocitos/metabolismo , Proteínas de Neoplasias/metabolismo , Policitemia Vera/metabolismo , Oclusión de la Vena Retiniana/metabolismo , Adhesión Celular , Células Endoteliales/patología , Eritrocitos/patología , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Policitemia Vera/patología , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Oclusión de la Vena Retiniana/patología , Trombosis/metabolismo , Trombosis/patología
7.
Diabetes Metab Syndr ; 11(4): 305-309, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27612394

RESUMEN

Advanced glycation end products (AGE) resulted from a reaction between free amino group of proteins and carbohydrates. This reaction is followed by oxidation and molecular rearrangement. Alternatively AGEs can be produced by glycolysis and oxidation. AGEs bind to a cellular receptor RAGE. RAGE engagement by ligands AGE, ß-amyloid peptide, and S100 calgranulin induces a stimulation of NADPH oxidase, reactive oxygen intermediate formation, NFκB activation and gene transcription. This cascade of reaction leads to an inflammatory reaction responsible for alteration of microvessels in the retina and the kidney. Blockade of RAGE by antibodies anti-RAGE, TTP488 (azeliragon), or rRAGE prevents or limits the deleterious effect of AGEs.


Asunto(s)
Productos Finales de Glicación Avanzada/efectos adversos , Productos Finales de Glicación Avanzada/metabolismo , Salud , Receptor para Productos Finales de Glicación Avanzada/agonistas , Animales , Humanos , Inflamación/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Transducción de Señal
8.
Blood ; 121(4): 658-65, 2013 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-23160466

RESUMEN

Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Eritrocitos/metabolismo , Janus Quinasa 2/metabolismo , Sistema del Grupo Sanguíneo Lutheran/metabolismo , Policitemia Vera/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Eritropoyetina/metabolismo , Proteínas de Unión al GTP rap1/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Adhesión Celular/genética , Moléculas de Adhesión Celular/genética , Línea Celular , Femenino , Humanos , Janus Quinasa 2/genética , Laminina/metabolismo , Sistema del Grupo Sanguíneo Lutheran/genética , Masculino , Ratones , Persona de Mediana Edad , Fosforilación , Policitemia Vera/genética , Transducción de Señal
9.
Clin Hemorheol Microcirc ; 53(1-2): 11-21, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-22941965

RESUMEN

Red blood cell (RBC) adhesion to endothelium can be studied in static and flow conditions. Increased RBC adhesion was first described in sickle cell disease. Several molecules were shown to be involved in this phenomenon: VCAM-1, α4ß1, Lu/BCAM, ICAM-4. In malaria, Plasmodium falciparum erythrocyte membrane protein1 binds to ICAM-1, PECAM-1 and facilitates the parasite dissemination. In diabetes mellitus augmented RBC adhesion is correlated to the severity of vascular complications. Glycated RBC band3 reacts with the endothelial Receptor for Advanced Glycation End products (RAGE). RAGE engagement induced endothelial cell dysfunction. In patients with Polycythemia Vera (PV), the most frequent myeloproliferative disorder, constitutive phosphorylation of RBC Lu/BCAM is responsible for an increased adhesion to endothelial cell laminin. Retinal vein occlusion (RVO) is a common cause of permanent visual loss. Spontaneous growth of erythroid precursors was observed in more than 25% of patients. RBC adhesion was enhanced and correlated to phosphatidyl serine (PS) expression on RBC. Anti-PS receptor blocked RVO RBC adhesion indicating that the counterpart of RBC PS is PS endothelial cell receptor. Erythrocyte adhesion is mediated by different molecule abnormalities in different diseases but is associated to a higher risk of thrombosis and vascular complications.


Asunto(s)
Anemia de Células Falciformes/sangre , Adhesión Celular/fisiología , Diabetes Mellitus/sangre , Eritrocitos/fisiología , Malaria Falciparum/sangre , Policitemia Vera/sangre , Oclusión de la Vena Retiniana/sangre , Anemia de Células Falciformes/tratamiento farmacológico , Animales , Moléculas de Adhesión Celular/metabolismo , Humanos , Hidroxiurea/uso terapéutico , Policitemia Vera/tratamiento farmacológico , Proteínas Protozoarias/sangre , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/sangre
11.
Clin Hemorheol Microcirc ; 45(2-4): 143-53, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20675894

RESUMEN

Elevated glucose concentration increases oxidation and Advanced Glycation End product (AGE) formation. The binding of circulatory AGEs or AGEs included in erythrocyte membrane to the receptor for AGEs (RAGE) generates in endothelial cells an oxidative stress and enhances the expression of inflammatory molecules. Engagement of RAGE by AGEs and subsequent signaling plays an important role in the development of diabetic complications. Soluble RAGE isoforms (sRAGE) neutralize the ligand-mediated damage by acting as a decoy. If the expression of RAGE is upregulated during the pathogenesis of inflammatory diseases, sRAGE mostly found decreased when complications ensue. By modulating RAGE isoform expression, it could be possible to reduce the incidence of complications. This review focused on the capability of Angiotensin Receptor Blockers (ARBs), which are used to treat patients with hypertension and/or diabetes, to modulate RAGE isoform expression because some data reported the interference with RAGE downstream. In this regard, three ARBs - irbesartan, telmisartan, candesartan cilexetil - were tested and provided evidence for their ability to inhibit in human endothelial cells the expression of membrane-bound and soluble RAGE isoforms induced by the inflammatory factor Tumor Necrosis Factor-alpha (TNF-alpha), demonstrating the potential benefits of these molecules in RAGE-oriented therapies. Modulating RAGE isoforms expression by correcting endothelial dysfunction is achievable by drugs already used for hypertension or diabetes treatment such as ARBs.


Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Antihipertensivos/farmacología , Receptores Inmunológicos/efectos de los fármacos , Bencimidazoles/farmacología , Benzoatos/farmacología , Compuestos de Bifenilo/farmacología , Humanos , Hipoglucemiantes/farmacología , Irbesartán , Isoformas de Proteínas , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/biosíntesis , Telmisartán , Tetrazoles/farmacología , Factor de Necrosis Tumoral alfa/farmacología
13.
Biorheology ; 46(1): 63-72, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19252229

RESUMEN

Red blood cell (RBC) adhesion to endothelium is increased in diabetes mellitus and is correlated with the severity of vascular complications. Microangiopathy is the most frequent complications in patients suffering from diabetes mellitus. Elevated glucose concentration increases the oxidation phenomenon and advanced glycation end product (AGE) formation. Plasma proteins, structural proteins and also RBC proteins can be glycated such as glycated hemoglobin and RBC membrane proteins. Interaction of plasmatic AGE or RBC bearing AGE with the receptor for AGE (RAGE) alters vascular function leading to a vascular hyperpermeability inflammatory reaction including oxidant stress and cytokine production. Reactive oxygen species (ROS) react with nitric oxide (NO) limiting its vasodilatory effect and NO synthase function is altered. All these factors may be at the origin of high blood pressure which is deleterious for the eye and kidney vasculature. AGE can act directly on vascular function but also through RAGE. AGE binding to RAGE alters endothelial cell function stimulating NADPH oxidase and reactive oxygen species production. Limiting oxidation, reducing AGE formation or interaction with RAGE is achievable by drugs already used for hypertension or diabetes, but new treatment by NO modulators may limit the deleterious effect of RBC adhesion to endothelium.


Asunto(s)
Diabetes Mellitus/sangre , Endotelio Vascular/metabolismo , Eritrocitos/metabolismo , Óxido Nítrico/metabolismo , Receptores Inmunológicos/metabolismo , Adhesión Celular , Membrana Eritrocítica/metabolismo , Productos Finales de Glicación Avanzada/sangre , Humanos , Receptor para Productos Finales de Glicación Avanzada
15.
J Soc Biol ; 201(2): 175-84, 2007.
Artículo en Francés | MEDLINE | ID: mdl-17978751

RESUMEN

Advanced glycation end-products (AGE) are a group of heterogeneous molecules found in higher levels during diabetes, end stage renal failure and aging. Vascular alteration is correlated with their accumulation as during retinopathy or glomerulosclerosis. Glycation of extracellular matrix proteins is associated with diabetic angiopathy. AGE stimulate endothelial cell via the interaction with the receptor RAGE, leading to an inflammatory state with increased adhesion molecule expression, chemoattractant factor and tissue factor production. RAGE activation by AGE triggers reactive oxygen species production by NADPH oxydase. Agents that inhibit AGE formation, stimulate their degradation or neutralize their binding to RAGE represent new approaches to limit the deleterious activities of AGE.


Asunto(s)
Endotelio Vascular/fisiopatología , Productos Finales de Glicación Avanzada/fisiología , Envejecimiento/fisiología , Diabetes Mellitus/fisiopatología , Proteínas de la Matriz Extracelular/fisiología , Humanos , Fallo Renal Crónico/fisiopatología
16.
Blood ; 110(3): 894-901, 2007 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-17412890

RESUMEN

Patients with polycythemia vera (PV) have a JAK2 (a cytosolic tyrosine kinase) mutation and an increased risk of vascular thrombosis related to red blood cell (RBC) mass and platelet activation. We investigated functional RBC abnormalities that could be involved in thrombosis. RBC adhesion to human umbilical vein endothelial cells (HUVECs) was measured by a radiometric technique and in a flow system by video microscopy, and adhesion molecule expression was determined using specific antibodies (against CD36, CD49d, ICAM-4, Lu/BCAM, CD147, and CD47) and flow cytometry in a group of 38 patients with PV and a group of 36 healthy volunteers. Adhesion of PV RBCs was 3.7-fold higher than that of normal RBCs (P < .001). Adhesion was inhibited when PV RBCs were incubated with anti-Lutheran blood group/basal cell adhesion molecule (Lu/BCAM) or when HUVECs were treated with anti-laminin alpha(5) and to a lesser extent with anti-alpha(3) integrin. Lu/BCAM was constitutively phosphorylated in PV RBCs. Transfection of K562 cells with JAK2 617V>F resulted in increased expression and phosphorylation of Lu/BCAM. Phosphorylation of Lu/BCAM increases RBC adhesion. Our results indicate that JAK2 mutation might be linked to Lu/BCAM modification and increased RBC adhesiveness, which may be a factor favoring thrombosis in PV.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Células Endoteliales/metabolismo , Eritrocitos Anormales/metabolismo , Proteínas de Neoplasias/metabolismo , Policitemia Vera/metabolismo , Trombosis/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos/farmacología , Antígenos CD , Adhesión Celular/efectos de los fármacos , Adhesión Celular/genética , Moléculas de Adhesión Celular/antagonistas & inhibidores , Células Endoteliales/patología , Eritrocitos Anormales/patología , Femenino , Humanos , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , Células K562 , Sistema del Grupo Sanguíneo Lutheran , Masculino , Persona de Mediana Edad , Mutación Missense , Proteínas de Neoplasias/antagonistas & inhibidores , Fosforilación/efectos de los fármacos , Activación Plaquetaria/efectos de los fármacos , Activación Plaquetaria/genética , Policitemia Vera/complicaciones , Policitemia Vera/genética , Policitemia Vera/patología , Trombosis/etiología , Trombosis/genética , Trombosis/patología , Venas Umbilicales/metabolismo , Venas Umbilicales/patología , Kalinina
17.
J Biol Chem ; 282(15): 10935-43, 2007 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-17303557

RESUMEN

In human, nine aminoacyl tRNA synthetases are associated with the three auxiliary proteins, p18, p38, and p43, to form a stable multiprotein complex. The p43 component, which has a potent tRNA binding capacity, is associated to the complex via its N-terminal moiety. This protein is also the precursor of the endothelial monocyte-activating polypeptide II (p43(EMAPII), corresponding to the C-terminal moiety of p43), a cytokine generated during apoptosis. Here we examined the cellular pathway that, starting from the p43 subunit of the complex, leads to this extracellular cytokine. We identified a new intermediate in this pathway, named p43(ARF) for Apoptosis-released Factor. This intermediate is produced in cellulo by proteolytic cleavage of endogenous p43 and is rapidly recovered in the culture medium. This p43 derivative was purified from the medium of human U937 cells subjected to serum starvation. It contains 40 additional N-terminal amino acid residues as compared with the cytokine p43(EMAPII) and may be generated by a member of the matrix metalloproteinase family. Recombinant p43(ARF) is a monomer in solution and binds tRNA with a Kd of approximately 6 nM, 30-fold lower than that of p43. Highly purified p43(ARF) or p43(EMAPII) do not stimulate the expression of E-selectin by human umbilical vein endothelial cells. Our results suggest that the cleavage of p43 and its cellular delocalization, and thus the release of this tRNA binding subunit from the complex, is one of the molecular mechanisms leading to the shut down of protein synthesis in apoptosis.


Asunto(s)
Aminoacil-ARNt Sintetasas/metabolismo , Antígenos de Neoplasias/metabolismo , Apoptosis , Factor Tu de Elongación Peptídica/metabolismo , Animales , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/aislamiento & purificación , Apoptosis/efectos de los fármacos , Células Cultivadas , Medio de Cultivo Libre de Suero , Selectina E/metabolismo , Esterasas/metabolismo , Regulación de la Expresión Génica , Humanos , Interleucina-3/farmacología , Ratones , Proteínas Mitocondriales , Factor Tu de Elongación Peptídica/genética , Factor Tu de Elongación Peptídica/aislamiento & purificación , Unión Proteica , Soluciones
18.
Blood ; 109(8): 3544-51, 2007 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-17158232

RESUMEN

The Lutheran (Lu) blood group and basal cell adhesion molecule (BCAM) antigens are both carried by 2 glycoprotein isoforms of the immunoglobulin superfamily representing receptors for the laminin alpha(5) chain. In addition to red blood cells, Lu/BCAM proteins are highly expressed in endothelial cells. Abnormal adhesion of red blood cells to the endothelium could potentially contribute to the vaso-occlusive episodes in sickle cell disease. Considering the presence of integrin consensus-binding sites in Lu/BCAM proteins, we investigated their potential interaction with integrin alpha(4)beta(1), the unique integrin expressed on immature circulating sickle red cells. Using cell adhesion assays under static and flow conditions, we demonstrated that integrin alpha(4)beta(1) expressed on transfected cells bound to chimeric Lu-Fc protein. We showed that epinephrine-stimulated sickle cells, but not control red cells, adhered to Lu-Fc via integrin alpha(4)beta(1) under flow conditions. Antibody-mediated activation of integrin alpha(4)beta(1) induced adhesion of sickle red cells to primary human umbilical vein endothelial cells; this adhesion was inhibited by soluble Lu-Fc and vascular cell adhesion molecule-1 (VCAM-1)-Fc proteins. This novel interaction between integrin alpha(4)beta(1) in sickle red cells and endothelial Lu/BCAM proteins could participate in sickle cell adhesion to endothelium and potentially play a role in vaso-occlusive episodes.


Asunto(s)
Anemia de Células Falciformes/metabolismo , Células Endoteliales/metabolismo , Eritrocitos Anormales/metabolismo , Integrina alfa4beta1/metabolismo , Sistema del Grupo Sanguíneo Lutheran/metabolismo , Anemia de Células Falciformes/complicaciones , Arteriopatías Oclusivas/metabolismo , Arteriopatías Oclusivas/patología , Adhesión Celular/efectos de los fármacos , Células Endoteliales/patología , Eritrocitos Anormales/patología , Humanos , Ligandos , Isoformas de Proteínas/metabolismo , Venas Umbilicales/metabolismo
19.
Perit Dial Int ; 26(6): 664-70, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17047233

RESUMEN

BACKGROUND: Conventional peritoneal dialysis fluids (PDFs) have been shown to damage the mesothelial layer and are associated with the development of peritoneal fibrosis and neoangiogenesis. New-generation PDFs have therefore been developed with physiological pH and reduced levels of glucose degradation products (GDPs), precursors of advanced glycation end products (AGEs). In this work, we evaluated and compared the improved biocompatibility of two new-generation PDFs (Balance and bicaVera) using mesothelial cell biology; we also compared them to a standard PDF (stay.safe) (all PDFs by Fresenius Medical Care, Fresnes, France). METHODS: stay.safe, Balance, and bicaVera were tested for their effect on human peritoneal mesothelial cell (HPMC) viability by measuring cell proliferation and apoptosis, and oncosis induction. The formation of AGEs was evaluated by immunoassay. Transforming growth factor beta-1 and vascular endothelial growth factor (VEGF) were immunoassayed in HPMC supernatants exposed to the above PDFs. RESULTS: At 15 g/L glucose concentration, HPMC exposure to bicaVera resulted in higher cell proliferation compared to Balance (p < 0.001) and stay.safe (p < 0.001). Compared to the lactate-buffered PDFs (Balance and stay.safe), oncosis was significantly lower in cells exposed to bicaVera (p < 0.05). bicaVera, containing lower amounts of GDPs, generated less AGE formation (p < 0.05) and VEGF production (p < 0.05) than either Balance or stay.safe. CONCLUSIONS: New-generation PDFs with physiological pH and lower GDP levels, especially if bicarbonate-buffered (bicaVera), have fewer in vitro toxic effects on mesothelial cells and may contribute to peritoneal preservation, thus improving long-term treatment of PD patients.


Asunto(s)
Bicarbonatos , Soluciones para Hemodiálisis , Lactatos , Diálisis Peritoneal , Tampones (Química) , Células Cultivadas , Células Epiteliales , Humanos , Peritoneo/citología
20.
Clin Hemorheol Microcirc ; 35(3): 379-86, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16899960

RESUMEN

Atherothrombotic complications are frequent in patients with type 2 diabetes. Red blood cells (RBC) from diabetic patients exhibited an increased adhesion which correlated to the extent of vascular complications. In the present study we have investigated the adhesive interactions of RBCs with endothelium, using flow-based assessments. RBCs and endothelial cells were unstimulated or stimulated using respectively adrenaline and TNFalpha. Adhesion assays were carried-out by drawing the RBC suspension through a glass microcapillary tube precoated by human umbilical vein endothelial cells. These microslides were then incorporated into a controlled flow system equipped with a computerized video-microscopic image analysis. RBCs from diabetic patients bind to endothelial cells and could withstand wall shear stresses above 0.1 Pa. After stimulation by TNFalpha the adhesion was 1.5-fold higher. Blocking experiments demonstrated that the adhesion was mediated by the receptor for AGE (RAGE). Adrenaline-treated RBCs showed a transient increase in adhesion at low shear stresses. Inflammatory mediators or catecholamine amplifying diabetic RBC adhesion may aggravate endothelial cell damages.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Agregación Eritrocitaria , Receptores Inmunológicos/fisiología , Anciano , Adhesión Celular , Células Cultivadas , Células Endoteliales/citología , Endotelio Vascular/citología , Epinefrina/farmacología , Eritrocitos/citología , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/genética , Factor de Necrosis Tumoral alfa/farmacología
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