Monozyten-chemotaktisches Protein-1 stimuliert die Abtötung von Leishmania major durch humane Monozyten
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We recently demonstrated that monocyte chemotactic protein 1 (MCP-1) is strongly expressed in lesions of patients with self-healing localized cutaneous leishmaniasis (LCL) whereas it is scarce in those of chronic diffuse cutaneous leishmaniasis (DCL). These results indicated that MCP-1 may contribute to the healing process. In the present study, we tested this assumption by analyzing the capacity of MCP-1 to trigger leishmanicidal activities in human monocytes. The results show that MCP-1 directly stimulates the elimination of intracellular Leishmania parasites by monocytes, a potential that correlates with the induction of reactive oxygen intermediates. Release of nitric oxide was not detected. To understand the crosstalk between the chemokine and Th cell-associated cytokines, we studied the influence of the Th1 cytokine IFN-* and the Th2 cytokine IL-4 on MCP-1-mediated activation of human monocytes. The data demonstrate for the first time that IFN-* and MCP-1 synergistically activate monocytes to clear intracellular parasites, whereas IL-4 abrogates the effect of MCP-1. Furthermore, IL-4 inhibits MCP-1 expression by infected monocytes, a finding that may explain the lack of MCP-1 in chronic lesions. In conclusion, the data suggest a novel model for macrophage activation in cutaneous leishmaniasis. In lesions of LCL, the synergistic action of MCP-1 and IFN-* may stimulate the killing of parasites by macrophages and promote healing, whereas the presence of IL-4 in DCL lesions may favor the suppression of MCP-1 and, together with the lack of IFN-, the progression of disease.
Laufzeit: von 01.1996 bis 06.1999