Cytokine-induced neutrophil chemoattractant in a rat model of lipopolysaccharide-induced acute lung injury.

To elucidate the role of major chemotactic factors, cytokine-induced neutrophil chemoattractant (CINC), leukotriene B4 (LTB4) and C5a in lipopolysaccharide (LPS)-induced acute lung injury in rat, we employed three reagents: anti-CINC-1 antibody, an LTB4 receptor antagonist (ONO-4057) and an anti-complementary agent (K-76COONa). Rats were divided into five groups: (1)control group; (2) LPS group, which received intratracheal instillation of LPS (100 microg/kg); (3) Anti-CINC group, which received intratracheal coinstillation of LPS with anti-CINC-1 antibody (1 mg/kg); (4) LTB4-Ra group, which received intravenous ONO-4057 (10 mg/kg) prior to intratracheal LPS; (5) Anti-C5a group, which received intravenous K-76COONa (100 mg/kg) prior to intratracheal LPS. The number of neutrophils in bronchoalveolar lavage (BAL) fluids 6 h after LPS instillation was significantly reduced in the Anti-CINC group, however, no reduction was found in either the LTB4-Ra group or Anti-C5a group. The levels of CINC-1, CINC-2alpha and CINC-3 in BAL fluids were significantly higher in the LPS group than in the saline-instilled control group. In vitro, the production of CINC-1 and CINC-3 from LPS-stimulated macrophages was significantly elevated compared to unstimulated macrophages 6 h later. The increase in CINC-2alpha production was markedly less than that of CINC-1 or CINC-3. These results indicate that CINCs, especially CINC-1 and CINC-3 play an important role in the recruitment of neutrophils to the lung in LPS-induced acute lung injury.