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Publication : Antiallergic cromones inhibit neutrophil recruitment onto vascular endothelium via annexin-A1 mobilization.

First Author  Yazid S Year  2010
Journal  Arterioscler Thromb Vasc Biol Volume  30
Issue  9 Pages  1718-24
PubMed ID  20558817 Mgi Jnum  J:179552
Mgi Id  MGI:5302634 Doi  10.1161/ATVBAHA.110.209536
Citation  Yazid S, et al. (2010) Antiallergic cromones inhibit neutrophil recruitment onto vascular endothelium via annexin-A1 mobilization. Arterioscler Thromb Vasc Biol 30(9):1718-24
abstractText  OBJECTIVE: To determine whether the inhibitory action of the antiallergic cromone "mast cell stabilizing" drugs on polymorphonuclear leukocyte (PMN) trafficking is mediated through an annexin-A1 (Anx-A1) dependent mechanism. METHODS AND RESULTS: Intravital microscopy was used to monitor the actions of cromones in the inflamed microcirculation. Reperfusion injury provoked a dramatic increase in adherent and emigrated leukocytes in the mesenteric vascular bed, associated with augmented tissue levels of myeloperoxidase. Nedocromil, 2 to 20 mg/kg, significantly (P<0.05) inhibited cell adhesion and emigration, as well as myeloperoxidase release, in wild-type but not Anx-A1(-/-) mice. Short pretreatment of human PMNs with nedocromil, 10 nmol/L, inhibited cell adhesion (P<0.05) in the flow chamber assay, and this effect was reversed by specific anti-AnxA1 or a combination of antiformyl peptide receptors 1 and 2, but not irrelevant control, antibodies. Western blotting experiments revealed that cromones stimulate protein kinase C-dependent phosphorylation and release Anx-A1 in human PMNs. CONCLUSIONS: We propose a novel mechanism to explain the antiinflammatory actions of cromones on PMN trafficking, an effect that has long puzzled investigators.
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