INTERLEUKIN-1-BETA EXPRESSION IS INDUCED BY ADHERENCE AND IS ENHANCEDBY FC-RECEPTOR BINDING TO IMMUNE-COMPLEX IN THP-1 CELLS

Adherence of monocytes to endothelial cells and subsequently to baseme nt membrane represents the initial steps in monocyte migration from th e vasculature to the interstitium. We investigated the role of adhesio n to endothelial cells and basement membrane in the induction of the c ytokine IL-1 beta, We demonstrated that mRNA for IL-1 beta is induced in adherent THP-1 cells, but not in a matrix-specific manner, Adherenc e to fibrinogen, however, causes an increase in mRNA for IL-1 beta, A background level of IL-1 beta mRNA induction was observed in cells adh erent to all matrices, including the non-specific human serum albumin substrate, as compared to non-adherent cells cultured in teflon trough s, In addition, antibodies to CD11a, CD11b, beta(1) integrin, VLA4, al pha v beta 3 (VNR), and ICAM-1 did not induce significant IL-1 beta mR NA when THP-1 cells were adherent to those immunoglobulins, THP-1 cell s adherent to immune complexes of anti-CD11a, anti-CD11b, anti-VLA4, a nti-VNR, and anti-ICAM-1 showed greater mRNA induction than cells adhe rent to primary antibodies alone, THP-1 cells adherent to non-specific immune complexes gave the highest level of mRNA induction, Secretion of IL-1 beta protein, measured by ELISA at 24 h, was greatest when cel ls were adherent to immobilized immune complexes or to fibrinogen, Our results demonstrate that a general adherence-induced increase in IL-1 beta gene expression is greatly enhanced by the presence of immune co mplex.