Intravenous interleukin-8 inhibits granulocyte emigration from rabbit mesenteric venules without altering L-selectin expression or leukocyte rolling.
Injection (i.v.) of the granulocyte chemoattractant/activator IL-8 has been shown to reduce neutrophil recruitment into dermal inflammatory sites in vivo. To further investigate the mechanism of this phenomenon, we examined the effect of i.v. [Ser-IL-8]72 (12-20 micrograms/kg) on leukocyte rolling and chemoattractant-induced emigration in mesenteric venules of New Zealand White rabbits and on expression of L-selectin (mAb LAM1-3) and CD18 (mAb 60.3) on circulating rabbit granulocytes. Within 1 min of IL-8 i.v., granulocytes virtually disappeared from carotid blood samples for approximately 5 min. Concomitantly, the flux of rolling leukocytes in mesenteric venules fell from 83 +/- 21 to 2 +/- 1 leukocytes/min. Both rolling leukocyte flux and systemic granulocyte count returned to or exceeded control values within less than 30 min. The chemoattractant/activator FMLP (0.15 microgram/kg i.v.) produced similar results. A second i.v. injection of IL-8 or FMLP, 90 min after the first challenge, had equipotent effects. Local extravascular application of IL-8 via micropipette close to a venule induced adhesion and emigration of 63 +/- 21 leukocytes per site before, but only 26 +/- 9 leukocytes per site 50 to 75 min after i.v. IL-8, when systemic granulocyte count and rolling leukocyte flux had reached or exceeded control values. This was not due to agonist-specific desensitization, because a similar reduction of leukocyte emigration was seen after FMLP i.v. Rabbit granulocytes circulating in vivo uniformly expressed near-control levels of L-selectin at all times between 3 and 360 min after IL-8 i.v. CD18 expression transiently increased after IL-8 i.v. and returned to base line by 90 min. These findings show that IL-8 i.v. reduces granulocyte recruitment to inflammatory sites by inhibiting function(s) necessary for transmigration that are independent of L-selectin and subsequent to rolling.
Ley
K
K
Freie Universität Berlin, Department of Physiology, Germany.
Baker
J B
JB
Cybulsky
M I
MI
Gimbrone
M A
MA
Luscinskas
F W
FW
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects* / Q000502:physiology; D007275:Injections, Intravenous; D016023:Integrins / Q000032:analysis; D016209:Interleukin-8 / Q000494:pharmacology*; D019041:L-Selectin; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011817:Rabbits; D014699:Venules
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016023:Integrins; D016209:Interleukin-8; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine