Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation.
1995; American Society for Clinical Investigation; Volume: 95; Issue: 5 Linguagem: Inglês
10.1172/jci117921
ISSN1558-8238
AutoresAndrew S. Weyrich, Thomas M. McIntyre, Rodger P. McEver, S M Prescott, Guy A. Zimmerman,
Tópico(s)Immune cells in cancer
ResumoAdhesion molecules that tether circulating leukocytes to endothelial cells may also transduce or modulate outside-in signals for cellular activation, providing an initial regulatory point in the inflammatory response.Adhesion of human monocytes to P-selectin, the most rapidly expressed endothe- lial tethering factor, increased the secretion of monocyte chemotactic protein-i (MCP-1) and tumor necrosis factor- a (TNF-a) by the leukocytes when they were stimulated with platelet-activating factor.Increased cytokine secretion was specifically inhibited by G1, an anti-P-selectin mAb that prevents P-selectin from binding to its ligand (P-selectin glycoprotein ligand-1) on myeloid cells.Moreover, tethering by P-selectin specifically enhanced nuclear translocation of nuclear factor-KB (NF-cB), a transcription factor required for expression of MCP-1, TNF-a, and other immediate-early genes.These results demonstrate that P-selectin, through its ligands on monocytes, may locally regulate cytokine secretion in inflamed tissues.(
Referência(s)