title: ICAM-1-expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia.
abstract: Intracellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein expressed on the cell surface of numerous cell types such as endothelial and epithelial cells, vascular smooth muscle cells, and certain leukocyte subsets. With respect to the latter, ICAM-1 has been detected on neutrophils in several clinical and experimental settings, but little is known about the regulation of expression or function of neutrophil ICAM-1. In this study, we report on the de novo induction of ICAM-1 on the cell surface of murine neutrophils by lipopolysaccharide (LPS), tumor necrosis factor, and zymosan particles in vitro. The induction of neutrophil ICAM-1 was associated with enhanced phagocytosis of zymosan particles and reactive oxygen species (ROS) generation. Conversely, neutrophils from ICAM-1-deficient mice were defective in these effector functions. Mechanistically, ICAM-1-mediated intracellular signaling appeared to support neutrophil ROS generation and phagocytosis. In vivo, LPS-induced inflammation in the mouse cremaster muscle and peritoneal cavity led to ICAM-1 expression on intravascular and locally transmigrated neutrophils. The use of chimeric mice deficient in ICAM-1 on myeloid cells demonstrated that neutrophil ICAM-1 was not required for local neutrophil transmigration, but supported optimal intravascular and extravascular phagocytosis of zymosan particles. Collectively, the present results shed light on regulation of expression and function of ICAM-1 on neutrophils and identify it as an additional regulator of neutrophil effector responses in host defense.
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;
authors.forename: Abigail
authors.initials: A
authors.lastname: Woodfin
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;
authors.forename: Martina
authors.initials: M
authors.lastname: Beyrau
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;
authors.forename: Mathieu-Benoit
authors.initials: MB
authors.lastname: Voisin
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;
authors.forename: James R
authors.initials: JR
authors.lastname: Whiteford
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Swammerdam Institute for Life Sciences Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Hordijk
authors.affiliation: Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors.forename: Nancy
authors.initials: N
authors.lastname: Hogg
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;
authors.forename: Sussan
authors.initials: S
authors.lastname: Nourshargh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects / Q000235:genetics
chemical_list: C090509:Icam1 protein, mouse; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1