The selective inhibition of beta 1 and beta 7 integrin-mediated lymphocyte adhesion by bacitracin.
Integrins play an important role in lymphocyte adhesion to cellular and extracellular components of their microenvironment. The regulation of such adhesion often involves changes in the functional state of the integrins rather than alterations in their expression levels. Although the functional basis for such transitions is unknown, a possible role for disulfide exchange might be postulated based on the observations that integrin function can be activated by bifunctional reducing agents or by Abs that react with areas adjacent to predicted long-range disulfide bonds in integrins. Recently, it has been reported that enzymes that catalyze disulfide exchanges such as protein disulfide isomerase (PDI) are present on the surface of lymphoid cells, raising the possibility that such enzymes might be involved in the control of lymphocyte adhesion. A number of inhibitors of PDI function were examined for their effects on integrin-mediated adherence of T cells. The results did not support role for PDI in the regulation of integrin function, as the inhibitors somatostatin A, tocinoic acid, dithiobisnitrobenzoic acid, and anti-PDI mAb did not interfere with adherence. However, one of the PDI inhibitors, bacitracin, selectively interfered with the beta1 integrin-mediated adherence of lymphoid cells to collagen, fibronectin, laminin, and VCAM-1, and with alpha4beta7-dependent adherence to fibronectin and to VCAM-1. In contrast, alpha(v)beta3- and alpha(L)beta2-mediated adherence were not inhibited. Thus, it appears that bacitracin may be a selective inhibitor of beta1 and beta7 integrin functions by an as yet unknown mechanism.
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Department of Immunology, University of Manitoba, Winnipeg, Canada.
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Wilkins
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D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D001414:Bacitracin / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002449:Cell Aggregation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D039641:Integrin beta Chains; D019012:Integrin beta1 / Q000502:physiology*; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology*; D019169:Jurkat Cells; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology
D004791:Enzyme Inhibitors; D039641:Integrin beta Chains; D019012:Integrin beta1; D016023:Integrins; C091368:integrin beta7; D001414:Bacitracin; D019704:Protein Disulfide-Isomerases