Neutrophil granulocytes: participation in homeostatic and reparative processes. Part I

Abstract

After exiting from the bone marrow (BM) into the circulation, mature neutrophil granulocytes undergo a set of sequential phenotypic and physiological changes collectively called “aging” in the absence of inflammation, by constitutively sensing prime signals from commensal microbiota and acquiring higher functional alertness in case of activation upon tissue damage or pathogen invasion. Physiological aging of blood neutrophils and their subsequent return to the BM result in signals modulating size and function of the hematopoietic niche. Circadian physiological infiltration of BM by neutrophils contributes to maintaining baseline level of circulating hematopoietic progenitor cells capable of regeneration and immune surveillance. Apart from the BM, neutrophils actively enter other healthy tissues, probably exerting some effects on their baseline physiologic state. Using lung tissue, it has been shown that neutrophils can “govern” action of gene set regulating cell growth, migration, proliferation, differentiation, and carcinogenesis. Neutrophils participate in destruction of endometrial tissues during desquamation phase as well as subsequent repair and physiological angiogenesis during proliferative phase of the menstrual cycle; promote wall rupture of the preovulatory ovarian follicle and oocyte exit; contribute to degradation and resorption of the corpus luteum in pregnancy failure; play an important physiological role in vascular remodeling in pregnant uterus and developing maternal immune tolerance to semi-allogeneic fetus. Neutrophils actively migrating to the surface of intestinal epithelium during local infection and/or damage stimulate epithelial restitution and recovery of its barrier function. On the other hand, neutrophils recruited into the oral cavity regulate quantitative and qualitative composition of microbial communities in oral biofilms, and ensure healthy state of periodontal structures. Being a major player and regulator in healing of skin wounds at early stage, inflammation, neutrophils not only destroy potential pathogens, but also participate in cleansing wounds from cell debris, produce cytokines, enzymes, and growth factors affecting further stages in repair process. Both apoptosis and NETosis underlying neutrophil death greatly contribute to wound healing. However, dysregulation and imbalance in both apoptosis and NETosis may lead to unfavorable consequences as well as developing chronic non-healing wounds.