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ICAM-1–expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia

Abigail Woodfin, Martina Beyrau, Mathieu-Benoit Voisin, Bin Ma, James R. Whiteford, Peter L. Hordijk, Nancy Hogg and Sussan Nourshargh

Key Points

  • Murine neutrophils can be stimulated by LPS to express de novo ICAM-1 in vitro and in murine models of endotoxemia in vivo.

  • Neutrophil ICAM-1 expression correlated with enhanced phagocytosis and ROS generation, and ICAM-1 deficiency caused defective phagocytosis.

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.

  • Submitted August 21, 2015.
  • Accepted November 25, 2015.
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