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 constitu tive IL-6 synthesis, stimulated endothelial cells to synthesize E-sele ctin, intracellular adhesion molecule-1, vascular cellular adhesion mo lecule-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 extravascula r compartment to surrounding endothelial cells will recruit more and a wider variety of leukocytes. The limiting signal is a soluble recepto r, not a cytokine.