Rega Institute for Medical Research, Laboratory of Molecular Immunology, University of Leuven, B-3000 Leuven, Belgium
Correspondence: Prof. G. Opdenakker, Rega Institute for Medical Research, Laboratory of Molecular Immunology, Minderbroedersstraat 10, B-3000 Leuven, Belgium. E-mail: ghislain.opdenakker{at}rega.kuleuven.ac.be
Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) and
gelatinase B are coexpressed at sites of inflammation, where an intense
interaction occurs between leukocytes and endothelial cells. To
investigate whether a functional link exists between PECAM-1 activation
and gelatinase B production, the regulatory role of PECAM-1, IFN-
,
IFN-ß, LPS, and PMA on the production of gelatinase B (MMP-9) was
studied in vitro in normal human umbilical vein endothelial cells
(HUVECs), human peripheral blood mononuclear cells (PBMCs), and in a
human monocytic leukemia cell line. In THP-1 cells, progelatinase B
levels were slightly up-regulated by immobilized PECAM-1-specific
monoclonal antibody (mAb) and soluble recombinant PECAM-1 when compared
with strong induction by LPS and PMA. IFN-ß inhibited the induced and
basal gelatinase B production but had no modulating effect on the
expression of PECAM-1. HUVECs mainly produced progelatinase A
(proMMP-2). Treatment with LPS and triggering of the endothelial cells
with PECAM-1 mAb or recombinant PECAM-1 had no effect on gelatinase A
or B production, whereas PMA stimulated the production of progelatinase
B. IFN-ß significantly up-regulated the expression of PECAM-1 in
HUVECs 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-ß reduced gelatinase B
secretion. IFN-ß did not alter PECAM-1 expression on PBMCs. Thus,
PECAM-1 and gelatinase B are differently regulated in leukocytes and
endothelial cells.
Key Words: multiple sclerosis • inflammation • cell-cell interaction • THP-1 • HUVEC • matrix metalloproteinase-9
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