NEUROPEPTIDES MODULATE A MURINE MONOCYTE/MACROPHAGE CELL LINE CAPACITY FOR PHAGOCYTOSIS AND KILLING OF LEISHMANIA MAJOR PARASITES

Abstract

Host-parasite interactions and their outcome constitute a critical and challenging step in disease establishment in cutaneous leishmaniasis. In the present in vitro study we investigated the possible modulating effects of both sensory and autonomic neuropeptides that normally exist in human and mouse skin, on the uptake and leishmanicidal capacity of macrophages on Leishmania (L.) major parasites, using a monocyte/macrophage murine cell line (Raw 264.7). The sensory neuropeptides somatostatin (SOM), calcitonin gene-related peptide (CGRP) and substance P (SP) suppressed the macrophage capacity for phagocytosing L. major promastigotes at different concentrations, 10⁻¹⁰–10⁻⁵M, however, the suppressive effect of SP does not reach a significant level. CGRP and SP enhanced the leishmanicidal capacity of macrophages at 10⁻⁷M, and 10⁻⁵ M, respectively, whereas SOM was without effect.

The autonomic neuropeptides vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) both suppressed the phagocytic and leishmanicidal capacities of macrophages at various concentrations, 10⁻¹⁰–10⁻⁵M.

The findings indicate that neuropeptides have modulating effects on macrophage-L. major interactions. These effects might be exerted by a direct action on macrophages or indirectly through induction of other mediators.