IL-1 activation of endothelium supports VLA-4 (CD49d/CD29)-mediated monocyte transendothelial migration to C5a, MIP-1 alpha, RANTES, and PAF but inhibits migration to MCP-1: a regulatory role for endothelium-derived MCP-1.
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 unactivated endothelium in response to macrophage inflammatory protein-1 alpha (MIP-1 alpha), RANTES, platelet-activating factor (PAF), or monocyte chemoattractant protein-1 (MCP-1) was completely inhibited (90%) by monoclonal antibodies (mAbs; 60.3) to CD18 of the CD11/CD18 complex on the monocyte and partially inhibited (by 75%) in response to C5a. When the HUVE was stimulated with IL-1 alpha (5 h, 0.1 ng/ml), monocyte migration in response to C5a, MIP-1 alpha, RANTES, or PAF was no longer inhibited by mAb to CD18. However, migration was blocked by the combination of mAb to the alpha 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-1 alpha 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-1 alpha-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Chuluyan
H E
HE
Department of Pediatrics, Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Schall
T J
TJ
Yoshimura
T
T
Issekutz
A C
AC
D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002634:Chemotaxis, Leukocyte; D015936:Complement C5a / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins; D009000:Monocytes / Q000166:cytology*; D015846:Monokines / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000502:physiology*; D016029:Receptors, Very Late Antigen / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines; D019040:E-Selectin; D007375:Interleukin-1; D016209:Interleukin-8; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D010972:Platelet Activating Factor; D015800:Protozoan Proteins; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015936:Complement C5a