Retrograde inflammatory signaling from neutrophils to endothelial cells by soluble interleukin-6 receptor alpha.
Endothelial cells initiate the inflammatory response by recruiting and activating leukocytes. IL-6 is not an agonist for this, but we found soluble IL-6 receptor alpha-subunit (IL-6Ralpha), with their constitutive IL-6 synthesis, stimulated endothelial cells to synthesize E-selectin, intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, IL-6, and IL-8, and to bind neutrophils. Neutrophils express significant amounts of IL-6Ralpha and upon stimulation shed it: this material activates endothelial cells through a newly constituted IL-6 receptor. Retrograde signaling from PMN activated in the extravascular compartment to surrounding endothelial cells will recruit more and a wider variety of leukocytes. The limiting signal is a soluble receptor, not a cytokine.
Modur
V
V
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112, USA.
Li
Y
Y
Zimmerman
G A
GA
Prescott
S M
SM
McIntyre
T M
TM
D000818:Animals; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D019040:E-Selectin; D015850:Interleukin-6; D016209:Interleukin-8; D019947:Receptors, Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1