[PDF][PDF] Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B …

AS Weyrich, TM McIntyre, RP McEver… - The Journal of …, 1995 - Am Soc Clin Investig
AS Weyrich, TM McIntyre, RP McEver, SM Prescott, GA Zimmerman
The Journal of clinical investigation, 1995Am Soc Clin Investig
Adhesion 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 endothelial tethering factor, increased the secretion of monocyte
chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) by the
leukocytes when they were stimulated with platelet-activating factor. Increased cytokine …
Adhesion 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 endothelial tethering factor, increased the secretion of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) 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-kappa B (NF-kappa B), a transcription factor required for expression of MCP-1, TNF-alpha, and other immediate-early genes. These results demonstrate that P-selectin, through its ligands on monocytes, may locally regulate cytokine secretion in inflamed tissues.
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The Journal of Clinical Investigation