Preliminary Exploration On The Function Of PMN Subpopulations And Analysis Of Gender Differences From The Occur To Resolution Process Of Acute Inflammation

Acute inflammation is an immediate,limited specific adaptive response caused by harmful stimuli.polymorphonuclear leukocytes（PMN）are the first responders in the immune response process.When the body is stimulated with pathogens,PMN would quickly migrate to the site of inflammation,swallow and kill pathogens,but excessive activation of PMN could also cause injury to the tissues.Studies have shown that its excessive activation is related to the immune response.Therefore,in recent years,many studies have begun to pay attention to the immune regulation and immunosuppressive functions of PMN.Annexin A1,an anti-inflammatory regulatory protein,could regulate the activation of immune cells such as PMN and macrophages,thereby effectively stops the acute inflammatory,and has an important immunomodulatory effect in inflammation.Studies have confirmed that there are obvious sex differences in the inflammation,but its specific regulatory mechanism is still unclear.Therefore,this study compares and analyzes the changes of PMN and Annexin A1+PMN proportion at different time points from inflammation occur to resolution in female and male acute peritonitis mice.Exploring the function of PMN and its subpopulations in acute inflammation,and preliminarily explaining the reasons for the difference between female and male inflammatory response,and providing a target for effective control of inflammatory response.This study found that:（1）PMN is the main cell population in the peritoneal lavage fluid of mice with peritonitis,which is divided into two subpopulations:Ly6G^high PMN and Ly6G^low PMN.（2）Ly6G^high PMN is the main PMN subpopulations when inflammation occurs,which can promote the occurrence of inflammation;while Ly6G^low PMN is a new PMN subpopulations that appeared in the peritoneal lavage fluid of peritonitis mice during the period of inflammation resolution,and the content of Ly6G^low PMN was higher when the inflammation resolution,indicating that it has a very key role in inflammation resolution.（3）Ly6G^high PMN and Ly6G^lowPMN cells are present in both the peritoneal lavage fluid and bone marrow,but they are not detected in the peripheral circulation,suggesting that Ly6G^low PMN in the inflammation site is generated at the inflammation site or is formed by the conventional PMN conversion at the inflammation site.（4）Annexin A1+PMN in the peritoneal lavage fluid mainly exists in the populations of Ly6G^low PMN cells,and it plays the role in the resolution stage of inflammation.In addition,the content of Annexin A1+PMN in the peritoneal lavage fluid is more than that of bone marrow and peripheral blood,indicating that Annexin A1+PMN mainly plays a key role in the site of inflammation.（5）Annexin A1+PMN is not exactly the same as Ly6G^low PMN,indicating that it is only a subpopulations of Ly6G^low PMN;and we speculate that Ly6G^low PMN plays a key role in the process of inflammation resolution through Annexin A1+PMN.（6）The time points of the peak period of inflammation in female and male mice are different.Male mice have a peak of inflammation at 6 h,and female mice have a peak of inflammation at 12 h.This indicating that there is a sex difference in the time point of PMN recruitment to the inflammation site.Males respond more quickly to inflammation than females.（7）The content of Ly6G^low PMN in the peritoneal lavage fluid of female mice is higher than that in male mice.It is speculated that this is the reason why the inflammation resolution in male mice more slowly than female mice.（8）The Ca²⁺concentration and lipid droplet content in Ly6G^low PMN are significantly higher than Ly6G^high PMN.Combined with the transcriptome differential gene enrichment analysis,it preliminarily shows that Ly6G^low PMN cell activity and regulatory functions are better than Ly6G^high PMN.