Acute peritonitis: adhesion molecules are regulated by a balance between endogenous and exogenous Annexin A1

Abstract

This study evaluated the effect of endogenous and exogenous annexin A1 (ANXA1) on cellmigration through the modulation of β2-integrin (CD11b) and L-selectin (CD62L) adhesionmolecules, using a classic model of peritonitis. Wild type (WT) and ANXA1 null (ANXA1null)mice, pretreated or not with the peptide Ac2-26 (ANXA1 N-terminal; 100 μg) received i.p.administration of zymosan (1.0 mg). After, blood, peritoneal exudates and mesenteries wereevaluated by biochemical and cellular analysis at 0, 4 and 24 h. Exogenous administration of Ac2-26 significantly decreased polymorphonuclear cells (PMN) trafficking and TNF-a release 4 h afterthe peritonitis process. In the inflammation resolution phase (24h), no difference was observedbetween animals treated with Ac2-26 or not. In addition to the change in cell recruitment,pretreatment with Ac2-26 significantly increased the expression of L-selectin and β2-integrin inblood PMN, but no effect was observed in these cells on ANXA1null. Ultrastructural analysisshowed co-localization between ANXA1 and adhesion molecules, particularly CD11b, in theplasma membrane and cytoplasm of neutrophils and endothelial cells. Administration of Ac2-26significantly reduced CD11b levels in these cells, but ANXA1null neutrophils had a highproportion of CD26L that was not modulated by the exogenous peptide. We envisage that theendogenous levels of ANXA1 are important to control the inflammatory response through CD62Lin PMN, whereas exogenous ANXA1 regulates the release of pro-inflammatory cytokines andCD11b in PMN and endothelial cells.