Incidence of myeloperoxidase deficiency in an area of northern Italy: histochemical, biochemical and functional studies

Cramer, Rita; Soranzo, Maria Rosa; Dri, Pietro; Rottini, G; Bramezza, M; Cirielli, S; Patriarca, Pierluigi

doi:10.1111/j.1365-2141.1982.tb07292.x

Cited by 47 publications

(27 citation statements)

References 17 publications

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“…The enhanced Superoxide anion production (lucigenin chemiluminescence) in myeloperoxidase deficient cells was described in the literature (15,16,23,24), and may be caused by two main reasons: Hasui et al (25) and Stendahl et al· (26) reported an enhanced phagocytosis of myeloperoxidase deficient granulocytes. This report stands in contrast to earlier observations of Cramer et al (27) and Larrocha et al (28), who demonstrated a normal phagocytic behaviour of the myeloperoxidase deficient granulocytes. We could confirm the results that myeloperoxidase deficient granulocytes are able to phagocytose more particles than normal ones (tab.…”

Section: Discussioncontrasting

confidence: 56%

Phagocytic Activity and Oxidative Burst of Granulocytes in Persons with Myeloperoxidase Deficiency

Gerber¹,

Kuçi²,

Zipfel³

et al. 1996

CCLM

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Summary:In the present study, phagocytosis and the oxidative metabolism of neutrophil granulocytes from five clinically healthy persons with different degrees of myeloperoxidase deficiency were investigated and compared to those of normal persons. The identification of individuals with myeloperoxidase deficiency was performed with the Bayer/Technicon H3 blood cell counter, which differentiates the leukocytes by measuring the peroxidase activity. Neutrophils of three out of five investigated myeloperoxidase deficient persons showed extremly low peroxidase indices (-53 and lower), but only the neutrophils of one person totally lacked myeloperoxidase. This was demonstrated by comparing myeloperoxidase mass concentration measured with an enzyme immunoassay, lack of HOC1 production, and was further confirmed by measuring luminol-and lucigenin-enhanced chemiluminescence. Characteristically, myeloperoxidase deficient granulocytes showed a strikingly decreased luminol-enhanced chemiluminescence while the lucigenin-enhanced chemiluminescence was significantly increased compared to normal granulocytes. Although there is a DNA sequence homology of about 70%, the activity of peroxidase in eosinophils was not affected in any myeloperoxidase deficient person investigated. Moreover, a person with a very rare defect of eosinophil peroxidase had completely normal myeloperoxidase activity. The lack of myeloperoxidase activity is compensated for by an increased phagocytic activity, an increased production of Superoxide anion (lucigeninchemiluminescence) and probably by an alternative metabolism of H 2 O 2 ; since persons lacking myeloperoxidase activity do not normally suffer from severe infections, H 2 O 2 is obviously metabolized to other reactive oxygen substrates than HOC1, e. g. to OH-radicals.

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Section: Discussioncontrasting

confidence: 56%

Phagocytic Activity and Oxidative Burst of Granulocytes in Persons with Myeloperoxidase Deficiency

Gerber¹,

Kuçi²,

Zipfel³

et al. 1996

CCLM

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“…Myeloperoxidase is a constituent of the azurophilic granule and is responsible for the greenish tinge seen in dense neutrophilic infiltrates. As a consequence of the deficient myeloperoxidase, neutrophil killing of some organisms is diminished early but is normal late in killing assays (64). HOCl is a potent microbicidal compound, but H 2 O 2 and granule contents may be primarily responsible for neutrophil killing in standard laboratory assays.…”

Section: Functional Neutrophil Disordersmentioning

confidence: 99%

Infections in Patients with Inherited Defects in Phagocytic Function

2003

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Patients with defects in phagocytic function are predisposed to intracellular microorganisms and typically have early dissemination of the infection. Recognition of the underlying disorder and aggressive antimicrobial therapy has been beneficial for the patients. Improved understanding of the pathophysiology has also affected patient management by allowing specific, targeted immunomodulatory intervention. The disorders described in this review are not common but have had a significant impact on our understanding of the role of phagocytic cells in host defense. Conversely, understanding the role of the neutrophil and macrophage in infection has benefited not just the patients described in this review but also other patients with similar disease processes

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“…8 MPO deficiency is reported to have an incidence of 1 in 2000-4000 in the United States and Europe and 1 in 55 000 in Japan. [9][10][11][12][13] Candida infections are common in MPO-deficient patients, especially in those that also develop diabetes. 9,[14][15][16][17][18] Occasionally, serious infectious or inflammatory complications have been observed in completely MPOdeficient patients as well.…”

Section: Introductionmentioning

confidence: 99%

Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity

Metzler

Fuchs

Nauseef

et al. 2011

Blood

622

533

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IntroductionMyeloperoxidase (MPO) is one of the most abundant proteins in neutrophils, accounting for 5% of the dry weight of the cell. 1 Stored in the azurophilic granules and released when neutrophils are stimulated, MPO catalyzes the oxidation of chloride and other halide ions in the presence of hydrogen peroxide 2,3 to generate hypochlorous acid and other highly reactive products that mediate efficient antimicrobial action. 4,5 Several inherited mutations and deletions in the gene encoding MPO result in decreased enzyme production and activity. 6,7 Using automated hematological devices, clinicians can distinguish between partial and complete MPO deficiencies. 8 MPO deficiency is reported to have an incidence of 1 in 2000-4000 in the United States and Europe and 1 in 55 000 in Japan. 9-13 Candida infections are common in MPO-deficient patients, especially in those that also develop diabetes. 9,14-18 Occasionally, serious infectious or inflammatory complications have been observed in completely MPOdeficient patients as well. 8 Consistently, MPO knockout mice are susceptible to particular bacterial and fungal infections. 19 Neutrophil extracellular traps (NETs) are part of the neutrophil response to microbes. Activated neutrophils die and release these structures composed of decondensed chromatin and antimicrobial proteins 20,21 that trap and inhibit a broad range of microbes. 22 Little is known about the molecular mechanism that regulates NET formation, making the antimicrobial role of NETs in vivo difficult to assess.Interestingly, neutrophils from chronic granulomatous disease (CGD) patients fail to make NETs. 20 CGD is caused by mutations that disrupt the ability of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate superoxide, which dismutates to hydrogen peroxide, the substrate of MPO. CGD patients are prone to recurrent and severe infections, as well as to persistent inflammation that can occur independently of infection. [23][24][25] NET formation by CGD neutrophils is restored by the addition of exogenous hydrogen peroxide, indicating that reactive oxygen species are required for NET formation. 20 Here we show that MPO is necessary for making NETs and suggest that defective NET formation may undermine host defense in patients lacking MPO. Methods Donor consentAll donors gave consent to blood drawing in accordance with the Declaration of Helsinki and to functional and genetic analysis. Samples were collected with approval from the ethical committees at each institution. Neutrophil isolationNeutrophils were isolated by centrifuging heparinized venous blood over Histopaque 1119 (Sigma-Aldrich) and subsequently over a discontinuous Percoll (Amersham Biosciences) gradient as described previously. 20 Cells were stored in Hank buffered salt solution (-) or Dulbecco phosphatebuffered saline (-), without calcium or magnesium, before experiments. NET formation and visualizationNeutrophils (5 ϫ 10 4 ) were seeded per well in 24-well tissue culture plates, in Hanks buffered salt solution (...

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Incidence of myeloperoxidase deficiency in an area of northern Italy: histochemical, biochemical and functional studies

Cited by 47 publications

References 17 publications

Phagocytic Activity and Oxidative Burst of Granulocytes in Persons with Myeloperoxidase Deficiency

Phagocytic Activity and Oxidative Burst of Granulocytes in Persons with Myeloperoxidase Deficiency

Infections in Patients with Inherited Defects in Phagocytic Function

Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity

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