INHIBITION OF PROLIFERATION AND STIMULATION OF MIGRATION OF ENDOTHELIAL-CELLS BY SECRETONEURIN IN-VITRO

Vascular cell responses in inflammation are affected by several neurop eptides of perivascular nerve fibers. Secretoneurin is a 33-amino acid peptide that is coreleased from these nerve endings with other proinf lammatory neuropeptides, eg, substance P and calcitonin gene-related p eptide. Furthermore, secretoneurin has been shown to be chemotactic fo r human skin fibroblasts and human blood monocytes in vitro and in viv o. An action on cellular components of the vascular wall is not yet re ported. We therefore investigated in vitro effects of this novel senso ry neuropeptide on endothelial cells. Secretoneurin exerted a potent a nd reversible inhibitory effect both on endothelial cell growth under low serum conditions (1% fetal calf serum) and endothelial cell growth factor-activated endothelial cell proliferation. We show in the prese nt study that secretoneurin exerts this effect on aortic (rat) and pul monary artery (bovine) endothelial cells, as well as venous (human umb ilical vein) endothelium. Endothelial cell chemotaxis was tested by me ans of three different migration assays employing nitrocellulose and p olycarbonate micropore filters. Secretoneurin consistently exhibited p otent chemoattractant activity. The effective concentrations for the o bserved effects were in the picomolar range. The combination of chemot actic and antiproliferative effects on endothelial cells suggests that secretoneurin may act as a regulatory factor of vascular cell functio ns.