Substance P alters the in vitro LPS responsiveness of bovine monocytes and blood-derived macrophages.

Neuromediators like substance P have a decisive influence on inflammatory processes via the neuroendocrine regulation circuit. The aim of the present study was therefore to evaluate the expression of the main substance P receptor NK-1R in cattle as well as the modulatory properties of substance P for bovine macrophages. The expression of NK-1R was detected in subsets of lymphocytes, granulocytes, monocytes and in vitro-generated macrophages (MdM). Stimulation of monocytes and MdM with lipopolysaccharide (LPS) for 3h did not alter the expression level of NK-1R. In vitro, the modulatory potential of substance P for monocytes and in vitro-generated blood-derived macrophages (MdM) was analysed. In MdM, generated in the presence of substance P, mRNA expression of chemokines, which are crucial for the attraction and activation of granulocytes and monocytes (CXCL8, CCL5) as well as the expression of IL-1beta, a classically pro-inflammatory cytokine were significantly elevated. After stimulation with LPS, MdM generated in the presence of substance P showed an elevated expression of CXCL8 and IL-1beta, while in SP-influenced monocytes only the expression of CCL5 was significantly upregulated after LPS stimulation. In addition, supernatants of MdM cultured in the presence of substance P induced neutrophil migration and inhibited both necrosis and apoptosis of neutrophil granulocytes. Thus, it has been shown that the modulation of the expression pattern of chemokines and cytokines in MdM by substance P has also functional relevance for the attraction and activation of other immune cells. In general, the modulation of sensor and effector functions by substance P suggests, that this neuromediator can alter the course of an inflammatory disease in cattle. Copyright 2010 Elsevier B.V. All rights reserved.