Antiallergic cromones inhibit neutrophil recruitment onto vascular endothelium via Annexin-A1 mobilization

Objective—To determine whether a mechanism exists that could operate on application of cromones, antiallertic "mast cell–stabilizing" drugs that release the anti-inflammatory protein annexin-A1 (Anx-A1) from U937 cells and inhibit polymorphonuclear leukocyte (PMN) trafficking, because PMNs can synthesize and release large amounts of Anx-A1. 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