The neuropeptide secretoneurin stimulates adhesion of human monocytes to arterial and venous endothelial cells in vitro

Monocytes appear to play a central role in inflammatory processes like atherogenesis or lung inflammation both as the progenitors of foam cells and as a potential source of factors mediating further inflammatory processes. However, signals mediating the influx of monocytes into the inflammatory focus remain partly unknown. Secretoneurin (SN) is a more recently characterised 33-amino acid neuropeptide that is co-released from afferent nerve endings together with substance P (SP) and calcitonin gene-related peptide (CGRP). Furthermore, SN has been shown to affect human fibroblast, endothelial, smooth muscle, eosinophil and monocyte functions in vitro. An activity of SN on monocyte adhesion to the vascular wall has not yet been reported. The aim of this study was to investigate whether the adhesion properties of human monocytes (U937 and Mono Mac-6) to endothelial cells could be influenced by SN. In an in vitro model of the vascular wall, incubation of arterial (rat aortic endothelial cells) and venous endothelial cells (immortalised human umbilical vein endothelial line: EA.hy 926) with SN resulted in a time- and concentration-dependent increase in monocyte adhesion with a maximal effect seen after 4–6 h at a concentration of 10−8 M SN. Increased monocyte adhesion seems not to be tissue-specific as SN-induced adhesion was observed on both arterial and venous endothelial cells. A specific antibody preparation against SN completely abolished increased monocyte adhesion toward SN-stimulated endothelium. Since adhesion was enhanced to a similar degree and with similar time kinetics as responses evoked by interleukin-1 (IL-1, 1 ng/ml) or lipopolysaccharide (LPS, 100 ng/ml), involvement of identical adhesion molecules can be suggested. Our observations provide substantial evidence that in inflammatory processes, SN might play a role in recruitment of monocytes to inflamed tissue. [Copyright &y& Elsevier]