Macrophage Inflammatory Protein-lalpha mediates Matrix Metalloproteinase-9 enhancement in human adherent monocytes fed with malarial pigment

<正>Objective:To investigate the role of macrophage inflammatory protein-1alpha(MIP-1 alpha) in the detrimental enhancement of matrix mnetalloproteinase-9(MMP-9) expression,release and activity induced by phagocytosis of malarial pigment(haemozoin,HZ) in human monocytes. Methods:Human adherent monocytes were unfed/fed with native HZ for 2 h.After 24 hours. MIP-1 alpha production was evaluated by ELISA in cell supernatants.Alternatively.HZunfed /fed monocytes were treated in presence/absence of anti-human MIP-1 alpha blocking antibodies or recombinant human MIP-lalpha for 15 h(RNA studies) or 24 h(protein studies): therefore,MMP-9 mRNA expression was evaluated in cell lysatcs by Real Time RT-PCR,whereas proMMP-9 and active MMP-9 protein release were measured in cell supernatants by Western blotting and gelatin zvmography.Results:Phagocytosis of HZ by human monocytes increased production of MIP-1 alpha.mRNA expression of MMP-9 and protein release of proMMP-9 and active MMP-9.All the HZ-enbancing effects on MMP-9 were abrogated by anti-human MIP- 1 alpha blocking antibodies and mimicked by recombinant human MIP-l alpha.Conclusions: The present work suggests a role for MIP-lalpha in the HZ-dependent enhancement of MMP-9 expression,release and activity observed in human monocytes.higbligbtiug new detrimental effects of HZ-triggered proinflammatory response by phagocytic cells in falciparum malaria.