Exogenous glutamine impairs neutrophils migration into infections sites elicited by lipopolysaccharide by a multistep mechanism

Glutamine (GLN) is the most abundant free amino acid in the body, and is considered as a conditionally essential amino acid under stress conditions, acting as an important modulator of the immune response. We here investigated the role of exogenous GLN treatment on leukocyte migration after the onset of endotoxemia and the intracellular mechanisms of GLN actions on neutrophils. Two in vivo models of endotoxemia caused by lipopolysaccharide of Escherichia coli (LPS) injection were carried out in male outbred Balb/C mice 2-3months old, as follow: (1) LPS (50g/kg) was intravenously injected 1h prior to intravenous injection of GLN (0.75mg/kg) and samples were collected 2h later to investigate the role of GLN on the acute lung inflammation; (2) LPS (1mg/kg) was intraperitoneally injected 1h prior to intravenous injection of GLN (0.75mg/kg) and samples were collected 18h later to measure the effects of GLN on local and later phases of inflammation in the peritoneum. Results showed that GLN administration reduced the number of neutrophils in the inflamed lungs, partially recovery of the reduced number of leukocytes in the blood; reduced adhesion molecules on lung endothelium and on circulating neutrophils. Moreover, GLN treatment diminished the number of neutrophils, levels of chemotactic cytokine CXCL2 in the inflamed peritoneum, and neutrophils collected from the peritoneum of GLN-treated mice presented lower levels of Rho, Rac, and JNK. Together, our data show novel mechanisms involved in the actions of GLN on neutrophils migration.