Role of Macrophage Inflammatory Protein (Mip)-Lα in Granulomatous Inflammation

Abstract

Macrophage inflammatory protein (MIP)-1 is a low MW, LPS-inducible monocyte and neutrophil chemotactic cytokine which may be important in inflammation and pulmonary granuloma formation. The present study examined the kinetic generation, and in vivo relevance of murine MIP- lα utilizing synchronous pulmonary Schistosoma mansoni egg granulomas. Antigenic MIP-lα was measured in 24 hr supernatants from whole granulomas cultured (700/ml) with or without soluble egg antigen (SEA) utilizing an ELISA developed in our laboratory. Intact primary granulomas isolated at various times of development from normal mice showed low backgroud levels of MIP- lα production (<1 ng/ml), however, when challenged with antigen demonstrated significant production of MIP-lα beginning at day 8 (2.6 ng/ml) and peaking at day 16 (16.8 ng/ml). Intact pulmonary granulomas isolated from acutely infected mice demonstrated high backgroud levels of MIP-lα production (peaking at day 2; 7.8 ng/ml). Likewise, background levels from chronic infection granulomas (day 2; 5.6 ng/ml) were similar to acute granulomas. Antigen stimulation increased expression of MIP- lα at all time points with granulomas from acutely infected (peaking at day 2; 16 ± 4.6 ng/ml) but not chronically infected (peaking at day 8; 3.45 ± 1.3 ng/ml) mice. Treatment of mice with polyclonal rabbit anti-mouse MIP-lα (6,125 ± 310 um2) abrogated 8 day primary pulmonary granuloma formation when compared to normal serum control group (12,704 ± 1154 um2). Anti-MIP-lα sera also decreased granuloma formation in lungs of acutely (4-day; 27,897 ± 2400 um2), but not chronically (4-day; 15257 + 1058 um2) infected mice compared to normal serum treated groups (36,010 ± 2507 and 17319 ± 1016 um2, respectively).KeywordsInfected MousePolyclonal RabbitAntigen StimulationSignificant ProductionGranuloma FormationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.