Role and Regulation of Chemokines in Rodent Models of Lung Inflammation.

Acute inflammatory lung injury has been induced in rats by intrapulmonary deposition of immunoglobulin G immune complexes or instillation of bacterial lipopolysaccaride. Several juxtaposed cysteine residue (CXC) chemokines (e.g., macrophage inflammatory protein 2 [MIP-2] and cytokine-induced neutrophil chemoattractant [CINC]) and CC chemokines (MIP-1alpha, MIP-1Beta, and monocyte chemoattractant protein-1 [MCP-1]) are upregulated in these acute injury models and appear in substantial amounts in bronchoalveolar (BAL) fluids during the inflammatory response. Antibody-induced blockade of either tumor necrosis factor alpha (TNFalpha ) or the complement activation product C5a results in significant reductions in BAL levels of chemokines, causing depressed inflammatory responses and diminished lung injury. These data suggest that both TNFalpha (a product of activated macrophages) and C5a participate as positive feedback mediators, resulting in maximal expression of chemokines. These chemokines are involved in recruitment of neutrophils and activation of tissue macrophages, the collective products of which cause acute lung injury mediated by the generation of oxidants and release of proteases.