Rat macrophage inflammatory protein-1alpha, a CC chemokine, acts as a neutrophil chemoattractant in vitro and in vivo.
Recombinant rat macrophage inflammatory protein-1alpha (rMIP-1alpha) at a concentration of 3x10(-8) M had strong neutrophil chemotactic activity, though the potency of rMIP-1alpha was less than that of cytokine-induced neutrophil chemoattractant (CINC)-1 at lower concentrations. In addition, rMIP-1alpha induced neutrophil chemotaxis in vivo when rMIP-1alpha was injected into the preformed air-pouch on the back of rats. The adhesion of rMIP-1alpha-treated neutrophils to fibrinogen significantly increased, reaching a maximum adhesion at 10(-8) M. Stimulation of neutrophils with rMIP-1alpha induced a transient increase in intracellular free [Ca2+] dose-dependently. rMIP-1alpha still induced an increase in the intracellular [Ca2+] of rat neutrophils stimulated first with CINC-1, CINC-3 or C5a, suggesting that rat neutrophils have a specific receptor for rMIP-1alpha. Supporting these findings, an additive increase in chemotactic potency was found when both rMIP-1alpha and CINC-were added to the lower wells of Boyden chamber in vitro. In addition, high levels of rMIP-1alpha were detected in the inflammatory site of air-pouch/carrageenan-induced inflammation in rats. Our results suggest that rMIP-1alpha acts as a neutrophil chemoattractant and, together with CINCs, plays an important role in infiltration of neutrophils into inflammatory sites in rats.
Takano
K
K
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Al-Mokdad
M
M
Shibata
F
F
Tsuchiya
H
H
Nakagawa
H
H
D000818:Animals; D002478:Cells, Cultured; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000276:immunology* / Q000494:pharmacology; D002630:Chemotactic Factors / Q000276:immunology / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology
D054407:Chemokine CCL4; D019742:Chemokines, CC; D002630:Chemotactic Factors; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins