Neutrophil recruitment in mast cell-dependent inflammation: inhibitory mechanisms of glucocorticoids

Abstract

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.

Estrogen Receptor Antagonist Fulvestrant (ICI 182,780) Inhibits the Anti-Inflammatory Effect of Glucocorticoids

“…Neutrophils were shown to express GR and ER receptor, suggesting a potential role of these receptors in the regulation of neutrophil function (Molero et al, 2002). Other studies have also demonstrated that GR may modulate leukocyte-endothelial cell interactions during inflammation through regulation of endothelial adhesion molecules (Schramm and Thorlacius, 2004). Furthermore, we found that the tissue damage induced by carrageenan was associated with high levels of the tissue thiobarbituric acid-reactant MDA, which is considered a good indicator of lipid peroxidation (Eiserich et al, 1996).…”

Role of the glucocorticoid‐induced leucine zipper gene in dexamethasone‐induced inhibition of mouse neutrophil migration via control of annexin A1 expression

“…Prevention of granulocyte transmigration is one of the mechanisms by which GCs exert their anti-inflammatory action (36,37). We have shown here that GILZ is necessary for GC-induced inhibition of neutrophil migration into sites of inflammation.…”

Pretreatment of cromolyn sodium prior to reperfusion attenuates early reperfusion injury after the small intestine ischemia in rats

“…Lindestrom and his colleagues [4] found the eosinophils and mast cells in rat ileum gradually increased after intestine ischemia (60 min)/reperfusion (60 min), and reported that the epithelium permeability increased significantly after ischemia-reperfusion. The researches of Kanwar and Schramm [5,6] were focused on mast cells stimulating neutrophil adherence, resupination, recruitment, and the intestinal mucosal injury. Boros [7] reported that mast cell degranulation prior to ischemia may induce a potentially protective mechanism in the small bowel mucosa and decrease ischemia-reperfusion injury in the dog.…”