CD177+ neutrophils alleviate acute pancreatitis-associated lung injury by protecting colonic barrier and restoring gut microbiota

Altered neutrophil infiltration and function are associated with the deterioration of acute pancreatitis (AP) and even AP-associated lung injury. Although CD177 is a marker of neutrophil activation, its role in AP remains largely unknown. To determine whether ablation of Cd177 could deteriorate colonic barrier dysfunction, changes in the gut microbiota, and AP-associated lung injury, Cd177 knock-out (KO), Cd177 conditional knock-out (cKO) in circulating neutrophils and pseudo-germ-free (antibiotic therapy, or ABX-treated) mouse models were used in this study. AP was induced in mice through injection of sodium taurocholate retrogradely into the pancreatic duct, then peripheral blood, pancreas, lung, colon tissues and fecal samples were collected at 24 h after induction, respectively. The mRNA and protein expression of certain genes and gut microbiota of mice were measured. Results indicated that both Cd177 KO and cKO increased serum amylase and lipase levels, exacerbated pathological damage, and impaired the integrity of the colonic mucosal barrier in AP mice, suggesting a protective role of neutrophil-derived CD177 in AP progression. In addition, ABX-treated mice alleviated AP-associated lung injury, demonstrating that gut microbiota dysbiosis may contribute to the deterioration of phenotypes. Moreover, ablation of Cd177 was associated with reduced abundance of gut microbiota species g_Atopostipes, downregulated Nos1ap expression in the lung and Sorbs1 expression in the colon, consequently aggravating the damage of colon and lung of mice with AP. It is concluded that Cd177+ neutrophils may ameliorate AP-associated lung injury through protecting colonic barrier and modulating certain gut microbiota and associated genes in mice.