Regulation of gelatinase B in human monocytic and endothelial cells by PECAM‐1 ligation and its modulation by interferon‐beta

Platelet endothelial cell adhesion molecule‐1 (PECAM‐1 or CD31) andgelatinase B are coexpressed at sites of inflammation, where an intenseinteraction occurs between leukocytes and endothelial cells. Toinvestigate whether a functional link exists between PECAM‐1 activationand gelatinase B production, the regulatory role of PECAM‐1, IFN‐γ,IFN‐β, LPS, and PMA on the production of gelatinase B (MMP‐9) wasstudied in vitro in normal human umbilical vein endothelial cells(HUVECs), human peripheral blood mononuclear cells (PBMCs), and in ahuman monocytic leukemia cell line. In THP‐1 cells, progelatinase Blevels were slightly up‐regulated by immobilized PECAM‐1‐specificmonoclonal antibody (mAb) and soluble recombinant PECAM‐1 when comparedwith strong induction by LPS and PMA. IFN‐β inhibited the induced andbasal gelatinase B production but had no modulating effect on theexpression of PECAM‐1. HUVECs mainly produced progelatinase A(proMMP‐2). Treatment with LPS and triggering of the endothelial cellswith PECAM‐1 mAb or recombinant PECAM‐1 had no effect on gelatinase Aor B production, whereas PMA stimulated the production of progelatinaseB. IFN‐β significantly up‐regulated the expression of PECAM‐1 inHUVECs but did not affect gelatinase secretion. Finally, in PBMCs, progelatinase B production was increased by soluble PECAM‐1 mAb, recombinant PECAM‐1, LPS, and PMA, whereas IFN‐β reduced gelatinase Bsecretion. IFN‐β did not alter PECAM‐1 expression on PBMCs. Thus, PECAM‐1 and gelatinase B are differently regulated in leukocytes andendothelial cells.