EXPRESSION AND PARTICIPATION OF EOTAXIN DURING MYCOBACTERIAL (TYPE-1)AND SCHISTOSOMAL (TYPE-2) ANTIGEN-ELICITED GRANULOMA-FORMATION

Eotaxin participation was analyzed during types 1 and 2 lung granuloma formation induced by embolizing Sepharose beads coupled to purified p rotein derivative (PPD) of Mycobacterium bovis or soluble Ags derived from Schistosoma mansoni eggs. Eotaxin was monitored by protein ELISA and semiquantitative reverse-transcriptase PCR mRNA analysis, Both typ es I and 2 granulomas released eotaxin, but levels were sixfold greate r (on day 4) in the type 2 than for the type 1 or foreign body granulo mas. Transcripts for eotaxin, IL-4, and CCR3 (eotaxin receptor) were a lso enhanced during type 2 granuloma formation. Anti-IL-4 treatment im paired eotaxin mRNA in lungs with type 2 granulomas, indicating that I L-4 promoted local eotaxin expression, In vivo, anti-eotaxin treatment caused modest reductions in the size of both types 1 and 2 lesions, w ith negligible effect on eosinophil recruitment. Surprisingly, anti eo taxin treatment abrogated IFN-gamma-producing cells in regional lymph nodes during the type 1 PPD response. Lymph nodes draining both types 1 and 2 lesions showed enhanced CCR3 mRNA,but this followed the time o f maximum eotaxin protein and mRNA expression. Correlative, in vitro s tudies revealed that graded doses of cotaxin increased IFN-gamma produ ction from PPD-sensitive regional lymph node cultures, while monocyte- chemotactic protein-1, an important macrophage chemoattractant, had th e opposite effect. These findings indicate that eotaxin expression is not limited to type 2 hypersensitivity granulomas, but also promotes I FN-gamma production during mycobacterial responses.