INTERACTIONS OF PROMONOCYTIC U937 CELLS WITH PROTEINS OF THE EXTRACELLULAR-MATRIX

Monocyte interaction with proteins of the extracellular matrix (ECM) i s regulated by expression of specific cell-surface receptors. 12-O-tet radecanoyl phorbol-13-acetate (TPA) has been shown to induce the promo nocytic cell line U937 to a more differentiated monocyte-like state. I n this study we have analysed the attachment of U937 cells to ECM prot eins and the effects of treatment with TPA on this process. Non-induce d U937 cells attach to fibronectin- and Matrigel-coated surfaces witho ut TPA stimulation, but TPA further increases adherence to these subst rates as measured by an enhanced binding and by the lower concentratio n of proteins needed in the substrate to achieve 50% of maximal cell a dhesion. Attachment to type I collagen was seen only with activated U9 37 cells, whereas no measurable attachment to bovine serum albumin, vi tronectin, and type IV collagen was detected. TPA-activated U937 cells showed a two-fold increase in the expression of the RGD-dependent int egrin receptors alpha3 and alpha5, and a reduction in the expression o f alpha4, another fibronectin-specific receptor, whereas the common be ta1 chain was unchanged. Attachment of U937 cells to fibronectin was p rimarily mediated by the alpha3 and alpha5 integrins, as revealed by t he ability of GRGDS peptides to inhibit attachment, whereas the CS-1 p eptide, containing the alpha4 binding site, was largely ineffective in blocking attachment.