Rat macrophage inflammatory protein-1 alpha , a CC chemokine, acts as a neutrophil chemoattractant in vitro and in vivo

• Published in: Inflammation Vol. 23; no. 5; pp. 411 - 424
• Main Authors: Takano, K, Al-Mokdad, M, Shibata, F, Tsuchiya, H, Nakagawa, H
• Format: Journal Article
• Language: English
• Published: 01-10-1999
• Subjects: macrophage inflammatory protein 1^a
• ISSN: 0360-3997
• DOI: 10.1023/a:1021908908833

Recombinant rat macrophage inflammatory protein-1 alpha (rMIP-1 alpha ) at a concentration of 3 x 10 super(-8) M had strong neutrophil chemotactic activity, though the potency of rMIP-1 alpha was less than that of cytokine-induced neutrophil chemoattractant (CINC)-1 at lower concentrations. In addition, rMIP-1 alpha induced neutrophil chemotaxis in vivo when rMIP-1 alpha was injected into the preformed air-pouch on the back of rats. The adhesion of rMIP-1 alpha -treated neutrophils to fibrinogen significantly increased, reaching a maximum adhesion at 10 super(-8) M. Stimulation of neutrophils with rMIP-1 alpha induced a transient increase in intracellular free [Ca super(2+)] dose-dependently. rMIP-1 alpha still induced an increase in the intracellular [Ca super(2+)] of rat neutrophils stimulated first with CINC-1, CINC-3 or C5a, suggesting that rat neutrophils have a specific receptor for rMIP-1 alpha . Supporting these findings, an additive increase in chemotactic potency was found when both rMIP-1 alpha and CINC-1 were added to the lower wells of Boyden chamber in vitro. In addition, high levels of rMIP-1 alpha were detected in the inflammatory site of air-pouch/carrageenan-induced inflammation in rats. Our results suggest that rMIP-1 alpha acts as a neutrophil chemoattractant and, together with CINCs, plays an important role in infiltration of neutrophils into inflammatory sites in rats.