THE ROLE OF MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA IN SCHISTOSOMA-MANSONI EGG-INDUCED GRANULOMATOUS INFLAMMATION

Macrophage inflammatory protein 1 alpha (MIP-1alpha) is a 6-8-kD, lipo polysaccharide-inducible monocyte and neutrophil chemotactic protein t hat may be important in acute and chronic inflammation. The present st udy determined the sequential production, source, and in vivo contribu tion of murine MIP-1alpha in synchronized Schistosoma mansoni egg pulm onary granuloma formation. Granulomas were examined under conditions o f primary, secondary vigorous, and secondary immunomodulated immunity. Secreted MIP-1alpha was measured in 24-h supernatants from intact gra nulomas (700/ml) cultured with or without soluble egg antigen (SEA). P rimary granulomas isolated from naive mice over a 16-d period showed l ow spontaneous MIP-1alpha production (<1 ng/ml). However, when primary granulomas were challenged with SEA, significant MIP-1alpha productio n was observed beginning at day 4 and peaking at day 16. Intact vigoro us (isolated from 8-wk-infected mice) and modulated (isolated from 20- wk-infected mice) secondary pulmonary granulomas demonstrated comparab le spontaneous MIP-1alpha production. Addition of SEA to vigorous stag e granulomas augmented expression of MIP-1alpha at all time points, wh ereas stimulated modulated stage granulomas did not increase productio n. The latter observation is likely related to endogenous immunoregula tory mechanisms reported for modulated stage animals. Immunohistochemi cal localization of MIP-1alpha in granuloma sections and cytocentrifug e preparations from vigorous lesions localized MIP-1alpha production t o macrophages within granulomas. Treatment of mice with rabbit anti-mo use MIP-1alpha antibodies significantly decreased 8-d primary granulom a formation (>40%) when compared with control mice. Anti-MIP-1alpha se ra also decreased vigorous (>20%), but not modulated granuloma formati on. These findings demonstrate that MIP-1alpha contributes to cellular recruitment during schistosome egg granuloma formation.