Exogenous carbon monoxide inhibits neutrophil infiltration in LPS-induced sepsis by interfering with FPR1 via p38 MAPK but not GRK2
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Xu Wang1, Weiting Qin1, Mingming Song1, Yisen Zhang1, Bingwei Sun1
1Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, China
Bingwei Sun, email: firstname.lastname@example.org
Keywords: sepsis, neutrophil, carbon monoxide, microarray genechip, FPR1
Received: January 26, 2016 Accepted: April 11, 2016 Published: April 28, 2016
Excessive neutrophil infiltration in vital organs is life-threatening to patients who suffer from sepsis. We identified a critical role of exogenous carbon monoxide (CO) in the inhibition of neutrophil infiltration during lipopolysaccharide (LPS)-induced sepsis. CO delivered from carbon monoxide-releasing molecule 2 (CORM-2) dramatically increased the survival rate of C57BL/6 mice subjected to LPS in vivo. CORM-2 significantly suppressed neutrophil infiltration in liver and lung as well as markers of inflammatory responses. Affymetrix GeneChip array analysis revealed that the increased expression of chemoattractant receptor formyl peptide receptor 1 (FPR1) may contribute to the excessive neutrophil infiltration. The under agarose migration assay demonstrated that LPS stimulation promoted migration to the ligand of FPR1, N-Formyl-Met-Leu-Phe (fMLP) but that CORM-2 treatment inhibited this promotion. Further studies demonstrated that CORM-2 internalized FPR1 by inhibiting p38 mitogen-activated protein kinase (MAPK) but not G protein-coupled receptor kinase 2 (GRK2), which may explain the inhibitory effect of CORM-2 on LPS-stimulated neutrophils. In summary, our study demonstrates that exogenous CO inhibits sepsis-induced neutrophil infiltration by interfering with FPR1 via p38 MAPK but not GRK2.
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