Department of Zoology, Gargi College, University of Delhi, Delhi, 11049, India.
Toxicology & Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
J Leukoc Biol. 2019 Jan;105(1):49-61. doi: 10.1002/JLB.4RU0418-161R. Epub 2018 Oct 4.
Neutrophils play a key role in innate immune responses against foreign intrusion and influence the subsequent instigation of adaptive immune response. Nitric oxide (NO) synthesized by neutrophil nitric oxide synthase (NOS) profoundly modulates their diverse physiological responsibilities furthermore encompassing pathological implications. Neutrophils are the active participants in diverse inflammatory and cardiovascular disorders but neutrophil nitric oxide synthase (NOS) remains enigmatic on various aspects. This review focuses on inducible NOS (iNOS) and makes an attempt to address its potential impact in neutrophil pathophysiology, their differentiation, functionality, and survival. We described the scenario from its expressional modulation, by pro- and anti-inflammatory cytokines governing the extent and duration of neutrophil immune response, to iNOS catalysis, the intracellular compartmentalization, and protein-protein interactions determining its microenvironment, activity and its contribution as a potential signaling protein apart from its role as signal transducer. Further, the relevance of investigating the unexplored facets of iNOS biology in neutrophils and possible prototypes of iNOS regulation is also exemplified in related cellular systems.
中性粒细胞在针对外来入侵的先天免疫反应中发挥关键作用，并影响随后适应性免疫反应的引发。中性粒细胞一氧化氮合酶（NOS）合成的一氧化氮（NO）深刻调节其多样化的生理功能，同时也包含病理意义。中性粒细胞是多种炎症和心血管疾病的积极参与者，但中性粒细胞 NOS 在各个方面仍然神秘莫测。本篇综述聚焦诱导型 NOS（iNOS），并尝试探讨其在中性粒细胞病理生理学、分化、功能和存活中的潜在影响。我们描述了从其表达调控的情况，由促炎和抗炎细胞因子调控中性粒细胞免疫反应的程度和持续时间，到 iNOS 催化、细胞内区室化以及决定其微环境、活性的蛋白-蛋白相互作用，及其作为潜在信号蛋白的作用，除了作为信号转导器的作用。此外，还举例说明了在相关细胞系统中研究中性粒细胞中 iNOS 生物学的未知方面和 iNOS 调节的可能原型的相关性。
