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 an d extracellular components of their microenvironment. The regulation o f 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 agent s or by Abs that react with areas adjacent to predicted long-range dis ulfide bonds in integrins. Recently, it has been reported that enzymes that catalyze disulfide exchanges such as protein disulfide isomerase (PDP) are present on the surface of lymphoid cells, raising the possi bility that such enzymes might be involved in the control of lymphocyt e adhesion, A number of inhibitors of PDI function were examined for t heir effects on integrin-mediated adherence of T cells. The results di d not support role for PDI in the regulation of integrin function, as the inhibitors somatostatin A, tocinoic acid, dithiobisnitrobenzoic ac id, and anti-PDI mAb did not interfere with adherence. However, one of the PDI inhibitors, bacitracin, selectively interfered with the beta( 1) integrin-mediated adherence of lymphoid cells to collagen, fibronec tin, laminin, and VCAM-1, and with alpha(4)beta(7)-dependent adherence to fibronectin and to VCAM-1. In contrast, alpha(v)beta(3)- and alpha (L)beta(2)-mediated adherence were not inhibited. Thus, it appears tha t bacitracin may be a selective inhibitor of beta(1) and beta(7) integ rin functions by an as yet unknown mechanism.