Matrix Proteins

The accumulation of mononuclear phagocytes at sites of chronic inflammation is dependent on an increase in the rate of extravasation of blood-borne monocytes through the vascular endothelium into the connective tissue. Once the monocytes have emigrated into the connective tissue, they may differentiate into tissue macrophages, presumably following interactions with extracellular matrix proteins. To study these processes, we tested the effects of cytokines and phorbol esters on the adhesion of U937 cells, a human monocyte-like cell line, to cultured endothelial cells (EC) and to matrix proteins. In the absence of cytokines, very few of the U937 cells adhered to EC (5 % or less in most experiments). When EC were pretreated for optimal periods of time (4-8 hr) with recombinant interleukin-i a (IL-i a), IL-i 3, tumor necrosis factor-a (TNFa), or lymphotoxin (LT; also known as TNF-3), 35-85 % of the U937 cells were able to bind. Interferon--y (IFN9) and interleukin-2 (IL-2) did not stimulate U937-EC binding, even though IFN-y was shown to increase EC adhesiveness for T lymphocytes. Phorbol esters also greatly stimulated U937-EC adhesion but, In this case, the increase was due to an action on the U937 cells. A monoclonal antibody (MAb), 60.3, against the CD1 i/CD18 family of leukocyte adhesio