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IL‐1 activation of endothelium supports VLA‐4 (CD49d/CD29)‐mediated monocyte transendothelial migration to C5a, MIP‐1α, RANTES, and PAF but inhibits migration to MCP‐1: a regulatory role for endothelium‐derived MCP‐1
Author(s) -
Chuluyan H. Eduardo,
Schall Thomas J.,
Yoshimura Teizo,
Issekutz Andrew C.
Publication year - 1995
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.58.1.71
Subject(s) - monocyte , cd18 , umbilical vein , chemotaxis , cell adhesion molecule , biology , microbiology and biotechnology , endothelium , intercellular adhesion molecule 1 , chemokine , monoclonal antibody , immunology , in vitro , inflammation , biochemistry , antibody , receptor , endocrinology
We investigated the effect of interleukin‐1 (IL‐1) activation of human umbilical vein endothelium (HUVE) on human monocyte transendothelial migration induced by chemotactic factors. Monocyte migration across unacdvated endothelium in response to macrophage inflammatory protein‐lα (MIP‐1α), RANTES, platelet‐activating factor (PAF), or monocyte chemoat‐tractant protein‐1 (MCP‐1) was completely inhibited (90%) by monoclonal antibodies (mAbs; 60.3) to CD 18 of the CD11/CD18 complex on the monocyte and partially inhibited (by 75%) in response to C5a. When the HUVE was stimulated with IL‐lα (5 h, 0.1 ng/ml), monocyte migration in response to C5a, MIP‐lα, RANTES, or PAF was no longer inhibited by mAb to CD18. However, migration was blocked by the combination of mAb to the (α 4 ‐integrin (CD49d) chain of very late antigen‐4 (CD49d(/CD29) with the mAb to CD18. In contrast to the above stimuli, activation of the HUVE with IL‐1α inhibited the transendothelial migration of monocytes in response to MCP‐1. mAbs to the adhesion molecules up‐regulated on HUVE by IL‐1, i.e., E‐selectin (CD62E), intercellular adhesion molecule‐1 (CD54) or vascular cell adhesion molecule‐1 (CD106), did not reverse the inhibitory effect. Transendothelial migration in response to MCP‐1 but not to C5a was inhibited by the treatment of monocytes with culture supernatant from IL‐1α‐stimulated (but not from unstimulated) HUVE. Such supernatant contained chemotactic activity for monocytes, and a mAb to MCP‐1 blocked the migration inhibitory effect of IL‐1 activation of the HUVE monolayer, as well as the chemotactic activity in the supernatant from IL‐1‐stimulated HUVE. The inhibitory effect on migration of IL‐1‐stimulated HUVE was specific for monocytes because polymorphonuclear leukocyte transendothelial migration in response to IL‐8 (a related chemokine) was not inhibited by IL‐1 activation of HUVE. These results demonstrate that: (1) C5a but not MCP‐1, MIP‐lα, RANTES, or PAF activates not only a CD 18‐dependent but also a VLA‐4‐dependent mechanism on monocytes, which mediates migration across unstimulated HUVE; (2) IL‐1 (tumor necrosis factor‐α or lipopolysaccharide) activation of HUVE results in efficient VLA‐4 (CD494/CD29)‐mediated monocyte transendothelial migration in response to C5a, RANTES, MIP‐1α, and PAF, in addition to the CD 18‐dependent pathway, but inhibits the response to MCP‐1; and (3) this selective inhibition is probably due to MCP‐1 production by the activated endothelium monolayer and may be one mechanism of down‐regulation by the endothelium of monocyte migration in response to extravascular MCP‐1. J. Leukoc. Biol. 58: 71–79,1995.