ROLE FOR MACROPHAGE INFLAMMATORY PROTEIN-2 IN LIPOPOLYSACCHARIDE-INDUCED LUNG INJURY IN RATS

Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that po ssesses chemotactic activity for neutrophils, Rat MIP-2 was cloned and expressed as a 7,9-kDa peptide that exhibited dose-dependent neutroph il chemotactic activity at concentrations from 10 to 250 nM, Rabbit po lyclonal Ab to the 7,9-kDa peptide showed reactivity by Western blot a nalysis and suppressed its in vitro chemotactic activity, Cross-desens itization chemotaxis experiments suggested that the chemotactic respon ses elicited by MIP-2 and the related chemokine, cytokine-induced neut rophil chemoattractant, may be mediated through a common receptor, Als o, chemotactic responses to human CRO-alpha were blocked by exposure o f human neutrophils to either GRO-alpha or rat MIP-2, suggesting conse rvation of this receptor-mediated response, After LPS instillation int o rat lung, mRNA for MIP-2 was up-regulated in a time-dependent manner , peaking at 6 h, MIP-2 protein was detected in bronchoalveolar lavage fluids of these animals and a significant amount of chemotactic activ ity present in these fluids was attributed to MIP-2, On the basis of i ntrapulmonary instillation of Ab to MIP-2, neutrophil accumulation in lungs after airway instillation of LPS was found to be MIP-2-dependent , These data indicate that MIP-2 plays a significant role in LPS-induc ed inflammatory response in rat lungs and is required for the full rec ruitment of neutrophils.