alpha 4 Integrins and sialyl Lewis x modulation in chronic Chagas disease: further evidence of persistent immune activation.
We have previously shown that titers of soluble platelet selectin (s-P-selectin) and soluble vascular cell adhesion molecule-1 (s-VCAM-1) were increased in sera of patients with chronic Trypanosoma cruzi infection. In this study, we analyzed the expression of CD49d-integrins, that bind to VCAM-1, and sialyl Lewis x (SLe(x)), which binds selectins, in peripheral blood lymphocytes of 27 patients with Chagas' disease at different levels of disease severity. Patients with a mild form of Chagas' disease showed a lower number of CD49d(+) cells, in comparison with those with severe chronic cardiopathy. Decreased levels of CD49d(+) cells were detected in CD3(-) cell populations. Conversely, SLe(x) expression was found to be decreased in patients with severe Chagas' disease. Levels of soluble platelet endothelial cell adhesion molecule-1 (s-PECAM-1) were significantly increased in the plasma of patients with severe Chagas' disease while unaltered levels of MCP-1 were recorded. These data show that VCAM-1 and P-Selectin ligands are differentially expressed during the chronic phase of the Trypanosoma cruzi infection. These findings also reinforce a role of the P-selectin/SLe(x) adhesion pathway rather than very late antigen-4 (VLA-4)/VCAM-1, in the pathogenesis of Chagas' disease.
Laucella
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Instituto Nacional de Parasitología Dr Mario Fatala Chabén, Ministerio de Salud y Acción Social, Buenos Aires, Argentina. slaucella@yahoo.com
Riarte
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Prado
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Zapata
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Segura
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D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D002598:Chagas Cardiomyopathy / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D018932:Chemokine CCL2 / Q000097:blood; D002908:Chronic Disease; D006801:Humans; D039441:Integrin alpha4; D016023:Integrins / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008875:Middle Aged; D009844:Oligosaccharides / Q000096:biosynthesis*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D000080506:Sialyl Lewis X Antigen; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018932:Chemokine CCL2; D016023:Integrins; D009844:Oligosaccharides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000080506:Sialyl Lewis X Antigen; D039441:Integrin alpha4