Shedding of soluble receptor for tumor necrosis factor alpha induced by M. leprae or LPS from human mononuclear cells.
Cell surface expression and release of the tumor necrosis factor receptor (TNFR type I) was analyzed after stimulation of peripheral blood mononuclear cells (PBMC) with Mycobacterium leprae (M. leprae) or lipopolysaccharide (LPS). A transient spontaneous expression of TNFR type I on the surface of PBMC was observed. Two hr after activation with LPS, a significant reduction of TNFR type I expression was detected: Release of TNFR type I by M. leprae or LPS-stimulated PBMC was evaluated with an enzyme-linked immunoabsorbent assay. This release occurred relatively later (20 to 40 hr) than the secretion of TNF alpha which reached high levels between 8 to 20 hr after activation. Thalidomide, a potent drug for the treatment of erythema nodosum leprosum episodes by inhibiting TNF alpha production, had no influence on the TNFR type I expression. Similar results were obtained with pentoxifylline. It is concluded that the release of TNFR type I by M. leprae or LPS-stimulated PBMC may counteract the pro-inflammatory activities of TNF alpha, by reducing the systemic toxicity of this cytokine in leprosy.
Santos
D O
DO
Department of Cellular and Molecular Biology, University Federal Fluminense, Niterói, Brasil.
Lorré
K
K
de Boer
M
M
Van Heuverswyn
H
H
D002478:Cells, Cultured; D003864:Depression, Chemical; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D013792:Thalidomide / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide