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The small GTPase Rap1b acts as a negative regulator of neutrophil recruitment to inflamed lung with acute lung injury

 

Neutrophils play key roles in the first line of cellular defense that is essential in inflammatory processes. However, the uncontrolled accumulation of neutrophils into lungs can cause acute lung injury (ALI), due to release of excessive toxic oxidants and proteases. The mechanism of molecular regulation of neutrophil migration and recruitment is barely understood. Kumar et al. found small GTPase Rap1b acts as a critical suppressor of neutrophil accumulation to inflamed lungs. The article was published in The Journal of Experimental Medicine.

 

High concentration of proinflammatory cytokines, secreted by accumulated immune cells such as neutrophils, often increase risk of death in ALI patients. Unfortunately, therapeutic strategy that interferes cytokine activities cannot decrease patients mortality rate, about 35%. In this study, researchers focused on molecular regulation of neutrophils accumulation to inflamed lung. In rap1b-deficient mice, neutrophil recruitment and susceptibility to endotoxin shock were enhanced, due to the increased transcellular migration of neutrophil through endothelial cell. In addition ,this process was mediated by enhanced PI3K-Akt pathway and invadopodia-like protrusions in vitro. Consistently, in vivo experiment showed the inhibition of Akt signaling suppressed aberrant Rap1b-deficient neutrophil migration and endotoxin shock in inflamed lung. These findings provide a view of molecular regulation of neutrophil recruitment, and suggest a potential clinical strategy for sever ALI patients.

 

Reference:
J Exp Med. 2014 Aug 25;211(9):1741-58. 

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