Macrophage chemotactic protein-1 and macrophage inflammatory protein-1α induce nitric oxide release and enhance parasite killing in Leishmania infantum-infected human macrophages

Chemokines are a group of structurally defined small proteins that act as chemoattractants for leukocytes and are involved in many different biological activities, including leukocyte activation for antimicrobial mechanisms. We studied the effect of the chemokines monocyte chemotactic protein (MCP)(-1) and macrophage inflammatory protein (MIP)-1alpha on nitric oxide release and parasitocidal ability of peripheral blood-derived human macrophages in vitro infected with Leishmania infantum, zymodeme MON1. In infected human macrophages, treatment with MCP-1 or MIP-1alpha significantly enhanced nitric oxide production and leishmanicidal ability, compared with untreated cells, to the same levels induced by interferon-gamma. Both nitric oxide release and parasitocidal ability of macrophages were significantly reduced by addition of L-N(G)monomethylarginine (L-NMMA), which is a competitive inhibitor of the L-arginine nitric oxide pathway. These data suggest that MCP-1 and MIP-1alpha mediate macrophage activation for nitric oxide release and subsequent parasite clearance, and thus may play a role in the containment of Leishmania infection.