Acute mast cell-dependent neutrophil recruitment in the skin is mediated by KC and LFA-1: inhibitory mechanisms of dexamethasone.
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.
Schramm
Rene
R
Department of Surgery, Malmö University Hospital, Sweden.
Schaefer
Thilo
T
Menger
Michael D
MD
Thorlacius
Henrik
H
D000818:Animals; D002450:Cell Communication; D054360:Chemokine CXCL1; D018925:Chemokines / Q000378:metabolism / Q000502:physiology*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000276:immunology*; D012867:Skin / Q000166:cytology
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D003907:Dexamethasone