The role of rat cytokine-induced neutrophil chemoattractants (CINCs) in inflammation

Abstract

Rat cytokine-induced neutrophil chemoattractants (CINCs) are the members of the CXC chemokine family. Four neutrophil chemokines, CINC-1, CINC-2α, CINC-2β and CINC-3, were purified from the conditioned medium of granulation-tissue culture. CINC-2α and CINC-2β differ only in the sequence of three carboxy-terminal residues and are produced by alternative splicing. CINC-3 had neutrophil chemotactic activity similar to that of CINC-1 and CINC-2, but induced greater calcium mobilization than CINC-1 and CINC-2. CINC-1, -2 and -3 induced calcium flux in CXCR2-transfected HEK293 cells. In addition, anti-CXCR2 serum inhibited neutrophil chemotactic activities of the three types of CINCs almost completely. These results indicate that rat CXCR2 is a unique receptor for CINC-1, -2 and -3. CINCs induced calcium mobilization through pertussis toxin-insensitive G-protein but induced chemotaxis through pertussis toxin-sensitive G-protein. CINC-1/-2 and CINC-3 may stimulate both G-proteins with distinct efficiency. The concentration of CINC-1 increased transiently in rat air pouch/lipopolysaccharide inflammation, whereas the CINC-2 level increased linearly. The number of infiltrated cells increased up to 8 h. The increase in cell number was correlated with the total concentration of CINC-1 and CINC-2. Northern blot analyses and enzyme-linked immunosorbent assay showed that CINC expression was very low in rat macrophages without stimulation and increased after lipopolysaccharide stimulation. These data suggest that CINCs are expressed by inflammatory cells such as macrophages at a site of inflammation and play important roles in neutrophil infiltration. © 2002 The Pharmaceutical Society of Japan.