Regulatory effects of eotaxin on acute lung inflammatory injury

Eotaxin, which is a major mediator for eosinophil recruitment into lung, has regulatory effects on neutrophil-dependent acute inflammatory injury triggered by intrapulmonary deposition of IgG immune complexes in rats. In this model, cotaxin mRNA and protein were up-regulated during the inflammatory response, resulting in cotaxin protein expression in alveolar macrophages and in alveolar epithelial cells. Ab-induced blockade of cotaxin in vivo caused enhanced NF-KB activation in lung, substantial increases in bronchoalveolar lavage levels of macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant (CINC), and increased MIP-2 and CINC mRNA expression in alveolar macrophages. In contrast, TNF-a levels were unaffected, and IL-10 levels fell. Under these experimental conditions, lung neutrophil accumulation was significantly increased, and vascular injury, as reflected by extravascular leak of I-125-albumin, was enhanced. Conversely, when recombinant cotaxin was administered in the same inflammatory model of lung injury, bronchoalveolar lavage levels of MIP-2 were reduced, as was neutrophil accumulation and the intensity of lung injury. In vitro stimulation of rat alveolar macrophages with IgG immune complexes greatly increased expression of mRNA and protein for MIP-2, CINC, MIP-1 alpha, MIP-1 beta, TNF-alpha, and IL-1 beta. In the copresence of cotaxin, the increased levels of MIP-2 and CINC mRNAs were markedly diminished, whereas MIP-1 alpha, MIP-1 beta, TNF-alpha, and IL-1 beta expression of mRNA and protein was not affected. These data suggest that endogenous cotaxin, which is expressed during the acute lung inflammatory response, plays a regulatory role in neutrophil recruitment into lung and the ensuing inflammatory damage.