Regulation of ICAM-1 in human neutrophils

Abstract

Intercellular cell adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein with a vital role in the immune response to pathogens. The expression pattern of ICAM-1 is wide-ranging, encompassing endothelial cells, epithelial cells and neutrophils. Recent work has characterized the role of ICAM-1 in murine neutrophils, but the function of human neutrophil ICAM-1 is incompletely understood. Herein, we investigated the expression and role of ICAMs in human neutrophils in vitro and in vivo. Our findings show clear expression of ICAM-1, -3 and -4 on peripheral blood-derived neutrophils and demonstrate that the pathogen-associated molecular pattern (PAMP) lipoteichoic acid (LTA) is an inducer of ICAM-1 expression in vitro. In vivo, neutrophils obtained from the pleural cavity of patients with a parapneumonic effusion display enhanced expression of ICAM-1 compared to peripheral blood- and oral cavity-derived neutrophils. Moreover, migration of peripheral blood-derived neutrophils across endothelial cells can upregulate neutrophil ICAM-1 expression. These findings indicate that PAMPs and/or cytokines, alongside transmigration, enhance neutrophil ICAM-1 expression at sites of inflammation. Mechanistically we observed that ICAM-1high neutrophils display elevated S. aureus phagocytic capacity. However, unlike murine neutrophils, ICAM-1 intracellular signaling in human neutrophils was not essential for phagocytosis of S. aureus and reactive oxygen species (ROS) generation. Taken together, these results have important implications for the regulation of neutrophil-mediated pathogen clearance.

Keywords: ICAM-1; Neutrophil; phagocytosis; pleural effusion.