Prevalence of Inherited Myeloperoxidase Deficiency in Japan

Nunoi, Hiroyuki; Kohi, Fumikazu; Kajiwara, Hideki; Suzuki, Kazuo

doi:10.1111/j.1348-0421.2003.tb03414.x

Cited by 25 publications

(14 citation statements)

References 34 publications

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“…However, the introduction of automated flow cytometry to clinical hematology laboratories radically changed recognition of the prevalence of MPO deficiency [113][114][115]. In contrast to inherited MPO deficiency being a rare occurrence, cytochemistry screening revealed a prevalence of one in 2000 -4000 healthy individuals in North America and Europe [116 -118], and one in 57,000 in Japan [119]. Furthermore, these data triggered a dramatic revision in the appreciation of the consequences of MPO deficiency.…”

Section: Mpo-deficient Neutrophilsmentioning

confidence: 99%

Myeloperoxidase: a front-line defender against phagocytosed microorganisms

Klebanoff

Kettle

Rosen

et al. 2013

Journal of Leukocyte Biology

586

465

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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 neutrophils--the first cellular responders to invading microbes--exert 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.

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Section: Mpo-deficient Neutrophilsmentioning

confidence: 99%

Myeloperoxidase: a front-line defender against phagocytosed microorganisms

Klebanoff

Kettle

Rosen

et al. 2013

Journal of Leukocyte Biology

586

465

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“…Family studies established that the patient’s MPO‐deficiency was hereditary (98) and resulted from complete absence of the MPO protein (100). More recently, the prevalence of MPO‐deficiency has been found to range from about 1/5000 in Italy (101) to 1/50 000 in Japan (102), and the deficiency can arise from various gene defects (101).…”

Section: West Coast Studiesmentioning

confidence: 99%

α‐Defensins in human innate immunity

Lehrer¹,

2011

Immunological Reviews

374

377

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Defensins are small, multifunctional cationic peptides. They typically contain six conserved cysteines whose three intramolecular disulfides stabilize a largely β-sheet structure. This review of human α-defensins begins by describing their evolution, including their likely relationship to the Big Defensins of invertebrates, and their kinship to the β-defensin peptides of many if not all vertebrates, and the θ-defensins found in certain non-human primates. We provide a short history of the search for leukocyte-derived microbicidal molecules, emphasizing the roles played by luck (good), preconceived notions (mostly bad), and proper timing (essential). The antimicrobial, antiviral, antitoxic, and binding properties of human α-defensins are summarized. The structural features of α-defensins are described extensively and their functional contributions are assessed. The properties of HD6, an enigmatic Paneth cell α-defensin, are contrasted with those of the four myeloid α-defensins (HNP1-4) and of HD5, the other α-defensin of human Paneth cells. The review ends with a decalogue that may assist researchers or students interested in α-defensins and related aspects of neutrophil function.

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“…Only two patients with MPO deficiency had been reported (Grignaschi et al, 1963;Undritz, 1966) prior 1969 when Lehrer and Cline described a young diabetic male with MPO deficiency and disseminated candidiasis and reports of MPO deficiency were infrequent until haematology laboratories adopted peroxidase staining and flow cytometry to identify and enumerate cells in peripheral blood. Subsequently, studies demonstrate that MPO deficiency occurs relatively commonly, affecting 1 in 2000 to 4000 healthy individuals in North America and Europe (Kitahara et al, 1981;Kutter et al, 1994;Kutter, 1998) and 1 in 57 000 in Japan (Nunoi et al, 2003). With the exception of sys-temic candidiasis in the presence of diabetes mellitus, few MPO-deficient patients with increased or unusual infections have been reported.…”

Section: Role For Mpo In the Antimicrobial Activity Of Intact Neutropmentioning

confidence: 99%

Myeloperoxidase in human neutrophil host defence

2014

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Summary Human neutrophils represent the predominant leucocyte in circulation and the first responder to infection. Concurrent with ingestion of microorganisms, neutrophils activate and assemble the NADPH oxidase at the phagosome, thereby generating superoxide anion and hydrogen peroxide. Concomitantly, granules release their contents into the phagosome, where the antimicrobial proteins and enzymes synergize with oxidants to create an environment toxic to the captured microbe. The most rapid and complete antimicrobial action by human neutrophils against many organisms relies on the combined efforts of the azurophilic granule protein myeloperoxidase and hydrogen peroxide from the NADPH oxidase to oxidize chloride, thereby generating hypochlorous acid and a host of downstream reaction products. Although individual components of the neutrophil antimicrobial response exhibit specific activities in isolation, the situation in the environment of the phagosome is far more complicated, a consequence of multiple and complex interactions among oxidants, proteins and their by‐products. In most cases, the cooperative interactions among the phagosomal contents, both from the host and the microbe, culminate in loss of viability of the ingested organism.

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Prevalence of Inherited Myeloperoxidase Deficiency in Japan

Cited by 25 publications

References 34 publications

Myeloperoxidase: a front-line defender against phagocytosed microorganisms

Myeloperoxidase: a front-line defender against phagocytosed microorganisms

α‐Defensins in human innate immunity

Myeloperoxidase in human neutrophil host defence

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