Retrograde inflammatory signaling from neutrophils to endothelial cells by soluble interleukin-6 receptor alpha

• Published in: The Journal of clinical investigation Vol. 100; no. 11; pp. 2752 - 2756
• Main Authors: Modur, V, Li, Y, Zimmerman, G A, Prescott, S M, McIntyre, T M
• Format: Journal Article
• Language: English
• Published: United States 01-12-1997
• Subjects: Animals; Cells, Cultured; E-Selectin - biosynthesis; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Humans; Inflammation; Intercellular Adhesion Molecule-1 - biosynthesis; Interleukin-6 - biosynthesis; Interleukin-8 - biosynthesis; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - metabolism; Rabbits; Receptors, Interleukin-6 - biosynthesis; Receptors, Interleukin-6 - metabolism; Signal Transduction; Solubility; Vascular Cell Adhesion Molecule-1 - biosynthesis
• ISSN: 0021-9738
• DOI: 10.1172/jci119821

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.