The role of macrophage inflammatory protein 1α in Schistosoma mansoni egg-induced granulomatous inflammation

Abstract

Macrophage inflammatory protein 1 α (MIP-1α) is a 6-8-kD, lipopolysaccharide-inducible monocyte and neutrophil chemotactic protein that may be important in acute and chronic inflammation. The present study determined the sequential production, source, and in vivo contribution of murine MIP-1α in synchronized Schistosoma mansoni egg pulmonary granuloma formation. Granulomas were examined under conditions of primary, secondary vigorous, and secondary immunomodulated immunity. Secreted MIP-1α was measured in 24-h supernatants from intact granulomas (700/ml) cultured with or without soluble egg antigen (SEA). Primary granulomas isolated from naive mice over a 16-d period showed low spontaneous MIP-1α production (<1 ng/ml). However, when primary granulomas were challenged with SEA, significant MIP-1α production was observed beginning at day 4 and peaking at day 16. Intact vigorous (isolated from 8-wk-infected mice) and modulated (isolated from 20-wk-infected mice) secondary pulmonary granulomas demonstrated comparable spontaneous MIP-1α production. Addition of SEA to vigorous stage granulomas augmented expression of MIP-1α at all time points, whereas stimulated modulated stage granulomas did not increase production. The latter observation is likely related to endogenous immunoregulatory mechanisms reported for modulated stage animals. Immunohistochemical localization of MIP-1α in granuloma sections and cytocentrifuge preparations from vigorous lesions localized MIP-1α production to macrophages within granulomas. Treatment of mice with rabbit anti-mouse MIP-1α antibodies significantly decreased 8-d primary granuloma formation (>40%) when compared with control mice. Anti-MIP-1α sera also decreased vigorous (>20%), but not modulated granuloma formation. These findings demonstrate that MIP-1α contributes to cellular recruitment during schistosome egg granuloma formation.