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-6R alpha), 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-6R alpha 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.