Cytolytically inactive terminal complement complex causes transendothelial migration of polymorphonuclear leukocytes in vitro and in vivo.
Intravital microscopy was used to monitor leukocyte traffic across rat mesenteric postcapillary venules induced by the inactive terminal complement (C) complex (iTCC) topically applied to ileal mesentery. Leukocytes started rolling within 15 minutes from the administration of iTCC, and by 1 hour they adhered almost completely to the endothelium emigrating from the vessels in the next 3 hours. C5a caused a similar, though less marked, effect, whereas boiled iTCC was inactive, excluding the contribution of contaminating lipopolysaccharide. The complex stimulated the migration of polymorphonuclear neutrophils (PMNs) across endothelial cells (ECs) in a transwell system after a 4-hour incubation of ECs with iTCC added to the lower chamber of the transwell, whereas a 30-minute incubation was sufficient for C5a and interleukin (IL)-8 to induce the passage of PMNs. C5a was not responsible for the effect of iTCC because this complex had no chemotactic activity and contained too small an amount of C5a to account for the transendothelial migration of PMNs. Similarly, the effect of iTCC was not mediated by IL-8 released by stimulated ECs because anti-IL-8 failed to inhibit the migration of PMNs induced by the complex. Unlike tumor necrosis factor-alpha, iTCC did not cause the redistribution of platelet-endothelial cell adhesion molecule-1 (PECAM-1), and PMN mobilization was partially blocked by anti-PECAM-1 antibodies.
Dobrina
Aldo
A
Dipartimento di Fisiologia e Patologia, Università di Trieste, the IRCCS Burlo Garofolo, Trieste, Italy.
Pausa
Mario
M
Fischetti
Fabio
F
Bulla
Roberta
R
Vecile
Elena
E
Ferrero
Elisabetta
E
Mantovani
Alberto
A
Tedesco
Francesco
F
D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D002630:Chemotactic Factors; D015936:Complement C5a / Q000494:pharmacology; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006358:Hot Temperature; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008643:Mesentery / Q000098:blood supply; D009504:Neutrophils / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology; D051381:Rats; D011921:Rats, Inbred WKY; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D014699:Venules
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D015938:Complement Membrane Attack Complex; D016209:Interleukin-8; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; D015936:Complement C5a