ANTIGEN-INDUCED EOSINOPHILIC LUNG INFLAMMATION DEVELOPS IN MICE DEFICIENT IN CHEMOKINE EOTAXIN

The mechanisms that regulate the selective infiltration of eosinophils in certain allergic diseases are still poorly understood. The CC chem okine eotaxin is a potent chemoattractant. highly specific for eosinop hils. Recent studies have implicated that eotaxin plays an important r ole in the recruitment of eosinophils in different inflammation proces ses. A number of other chemokines. cytokines, and chemoattractants als o have chemotactic activities for eosinophils and some of them present high selectivity for eosinophils. To further study the role of eotaxi n in inflammation, we generated mutant mice with the eotaxin gene disr upted and replaced by the Escherichia coil beta-galactosidase gene. Th ese: mice developed normally and had no histologic or hematopoietic ab normalities. Furthermore, our studies showed that the lack of eotaxin did not affect the recruitment of eosinophils in the inflammation mode ls induced by Sephadex beads and thioglycollate, as well as in an expe rimental lung eosinophilia model induced by ovalbumin aerosol challeng e, even at the onset of the inflammatory response. The replacement of the eotaxin gene by the beta-galactosidase gene provided a useful mark er to monitor the activity of the eotaxin promoter under normal condit ions and after antigen challenges. Immunohistochemical staining sugges ted that endothelial cells were the major sources of eotaxin expressio n. (C) 1998 by The American Society of Hematology.