title: Retrograde inflammatory signaling from neutrophils to endothelial cells by soluble interleukin-6 receptor alpha.
abstract: 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.
authors.affiliation: Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: V
authors.initials: V
authors.lastname: Modur
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: G A
authors.initials: GA
authors.lastname: Zimmerman
authors.forename: S M
authors.initials: SM
authors.lastname: Prescott
authors.forename: T M
authors.initials: TM
authors.lastname: McIntyre
mesh_terms: 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
chemical_list: D019040:E-Selectin; D015850:Interleukin-6; D016209:Interleukin-8; D019947:Receptors, Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1