Neutrophil recruitment in mast cell-dependent inflammation: inhibitory mechanisms of glucocorticoids.
Mast cells are strategically localized along the microvasculature in tissues in close contact with the external environment, such as the skin, lung and intestines. By releasing a multi-faceted spectrum of proinflammatory mediators, such as cytokines and chemokines, mast cells have the capacity to coordinate trafficking of leukocytes. Mast cells play a pathophysiological role in numerous inflammatory diseases as diverse as hypersensitivity reactions, ischemia/reperfusion injury and rheumatoid arthritis. On the other hand, mast cells act also as tissue sentinels and are critically involved in the host defensive response against microbial infection by stimulating neutrophil recruitment. Glucocorticoids are powerful agents frequently used in mast cell-dependent diseases, although the anti-inflammatory mechanisms of these compounds are not completely understood at present. In order to circumvent steroid-associated side-effects and develop more specific therapeutics, numerous studies have examined the mechanisms underlying glucocorticoid inhibition of mast cell-dependent neutrophil recruitment. Based on recent findings, it may be suggested that glucocorticoids selectively inhibit the expression and function of certain adhesion molecules and chemokines. This review summarizes current insights into the underlying mechanisms of mast cell-regulated tissue accumulation of neutrophils and the inhibitory effects of glucocorticoids.
Schramm
R
R
Department of Thoracic and Cardiovascular Surgery, University Hospital Homburg/Saar, University of Saarland, Germany. reneschramm@hotmail.com
Thorlacius
H
H
D000818:Animals; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D005938:Glucocorticoids