Myeloperoxidase: a front-line defender against phagocytosed microorganisms

Journal of Leukocyte Biology

Christine C. Winterbourn  and²  Seymour J. Klebanoff¹  Henry Rosen¹  Anthony J. Kettle²  William M. Nauseef³ 

[1] Department of Medicine, University of Washington, Seattle, Washington, USA; Centre for Free Radical Research, Department of Pathology, University of Otago Christchurch, Christchurch, New Zealand;Iowa Inflammation Program and Department of Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Coralville, Iowa, USA Department of Medicine, University of Washington, Seattle, Washington, USA;

关键词: innate immunity;    host defense;    phagosomes;    neutrophils;   

DOI  :  10.1189/jlb.0712349

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Successful immune defense requires integration of multiple effector systems to match the diverse virulence properties that members of the microbial world might express as they initiate and promote infection. Human neutrophilsthe first cellular responders to invading microbesexert most of their antimicrobial activity in phagosomes, specialized membrane-bound intracellular compartments formed by ingestion of microorganisms. The toxins generated de novo by the phagocyte NADPH oxidase and delivered by fusion of neutrophil granules with nascent phagosomes create conditions that kill and degrade ingested microbes. Antimicrobial activity reflects multiple and complex synergies among the phagosomal contents, and optimal action relies on oxidants generated in the presence of MPO. The absence of life-threatening infectious complications in individuals with MPO deficiency is frequently offered as evidence that the MPO oxidant system is ancillary rather than essential for neutrophil-mediated antimicrobial activity. However, that argument fails to consider observations from humans and KO mice that demonstrate that microbial killing by MPO-deficient cells is less efficient than that of normal neutrophils. We present evidence in support of MPO as a major arm of oxidative killing by neutrophils and propose that the essential contribution of MPO to normal innate host defense is manifest only when exposure to pathogens overwhelms the capacity of other host defense mechanisms.

【 授权许可】

Unknown