Acute mast cell-dependent neutrophil recruitment in the skin is mediated by KC and LFA-1: inhibitory mechanisms of dexamethasone

Abstract

This study examined adhesive and signaling pathways and anti-inflammatory mechanisms of dexamethasone in acute mast cell-dependent neutrophil recruitment in the skin in mice. Mast cell activation dose- and time-dependently triggered influx of predominately neutrophils and secretion of cytokine-induced neutrophil chemoattractant (KC). Neutralization of KC attenuated neutrophil recruitment upon mast cell activation. Mast cell activation- and KC-induced neutrophil responses were significantly decreased in lymphocyte function-associated antigen-1 (LFA-1)-deficient mice. Dexamethasone inhibited neutrophil accumulation elicited by mast cell activation. It is interesting that dexamethasone significantly reduced the mast cell-dependent secretion of KC, whereas neutrophil recruitment induced by exogenous KC was insensitive to dexamethasone treatment. Thus, KC is a fundamental mediator of neutrophil recruitment in acute mast cell-dependent skin inflammation, and mast cell activation- and KC-induced neutrophil responses are LFA-1-dependent. Moreover, dexamethasone inhibits mast cell-regulated skin infiltration of neutrophils mainly by attenuating KC secretion. Thus, this study elucidates important interactions between chemokines and adhesion molecules in mast cell-dependent neutrophil recruitment and provides new insight into mechanisms of dexamethasone in skin inflammation.