Neutrophil accumulation induced by bacterial lipopolysaccharide: effects of dexamethasone and annexin 1

Annexin 1 (ANX-1) can reduce leucocyte migration in response to cytokines a nd chemokines in some rodent models of inflammation. However, its effective ness against an inflammatory stimulus as strong as bacterial lipopolysaccha ride (LPS) is unknown. Thus, we have examined whether ANX-1 can modulate LP S-induced neutrophil accumulation in the rat, as assessed by intravital mic roscopy and by myeloperoxidase (MPO) assay. The anti-inflammatory glucocort icoid, dexamethasone (DEX) was also studied for comparison. LPS superfusion induced adhesion of leucocytes to the endothelium and a subsequent increas e in emigration from rat post-capillary venules over 2 h as assessed by int ravital microscopy. Either ANX-1 or DEX was able to attenuate this adhesion and emigration of leucocytes. MPO activity in the lung, kidney and ileum w as elevated after a 6-h exposure to LPS (intraperitoneal), indicating accum ulation of neutrophils in these tissues. DEX attenuated the LPS-induced inc rease in MPO in the ileum but had no effect on MPO in the lungs or kidneys. This would suggest that the underlying mechanism by which neutrophils accu mulate in the ileum, and more generally in the gastrointestinal compartment , is different from other vascular beds. ANX-1 had no effect on the LPS-ind uced increase in MPO activity in any of the tissues studied. Thus, from the se data, ANX-1 appears to reduce leucocyte adhesion and emigration induced by a short-term (2 h), but not a longer (6 h) exposure to LPS.