Granule enzymes of polymorphonuclear neutrophils: A phylogenetic comparison

Rausch, PG; Moore, TG

doi:10.1182/blood.v46.6.913.913

Cited by 174 publications

(47 citation statements)

References 24 publications

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“…Clinical and histologic characteristics of patients with biopsy-proven NASH and control patients are provided in the Limitations of our study include that no NASH model entirely replicates all human pathologic features because the pathogenesis remains incompletely understood. However, we have addressed this shortcoming by using two different animal models that mimic different aspects of the disease (16,17) and by confirming results in human mouse MPO is only about 10%-20% as active as human MPO (37), the MR signal would likely be even stronger at translation to humans. Compatible with this, we found a CNR of 2.6 in human liver biopsy samples compared with 1.3-1.8 in mouse experiments, but differences in the experimental setup (in vivo animal vs ex vivo biopsy sample imaging) may also contribute to this difference.…”

Section: Mpo-gd Molecular Mr Imaging Detection Of Elevated Mpo Activimentioning

confidence: 87%

Molecular MR Imaging of Myeloperoxidase Distinguishes Steatosis from Steatohepatitis in Nonalcoholic Fatty Liver Disease

et al. 2017

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Purpose To test whether MPO-Gd, an activatable molecular magnetic resonance (MR) imaging agent specific for myeloperoxidase (MPO) activity, could detect MPO activity in nonalcoholic steatohepatitis (NASH) mouse models and human liver biopsy samples. Materials and Methods In this study, 20 leptin receptor-deficient and three MPO knockout mice were injected with endotoxin (lipopolysaccharide) or fed a methionine and choline-deficient (MCD) diet to induce experimental NASH and underwent MR imaging with MPO-Gd. Saline-injected and control diet-fed leptin receptor-deficient mice were used as respective controls. MPO protein and activity measurements and histologic analyses were performed. Eleven human liver biopsy samples underwent MPO-Gd-enhanced MR imaging ex vivo and subsequent histologic evaluation. Results were compared with Student t test or Mann-Whitney U test. Results With endotoxin, a significantly increased contrast-to-noise ratio (CNR) was found compared with sham (mean CNR, 1.81 [95% confidence interval {CI}: 1.53, 2.10] vs 1.02 [95% CI: 0.89, 1.14]; P = .03) at MPO-Gd MR imaging. In the diet-induced NASH model, an increased CNR was also found compared with sham mice (mean CNR, 1.33 [95% CI: 1.27, 1.40] vs 0.98 [95% CI: 0.83, 1.12]; P = .008). Conversely, CNR remained at baseline in NASH mice imaged with gadopentetate dimeglumine and in MPO knockout NASH mice with MPO-Gd, which proves specificity of MPO-Gd. Ex vivo molecular MR imaging of liver biopsy samples from NASH and control patients confirmed results from animal studies (mean CNR for NASH vs control patients, 2.61 [95% CI: 1.48, 3.74] vs 1.29 [95% CI: 1.06, 1.52]; P = .004). Conclusion MPO-Gd showed elevated MPO activity in NAFLD mouse models and human liver biopsy samples. RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on April 6, 2017.

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Section: Mpo-gd Molecular Mr Imaging Detection Of Elevated Mpo Activimentioning

confidence: 87%

Molecular MR Imaging of Myeloperoxidase Distinguishes Steatosis from Steatohepatitis in Nonalcoholic Fatty Liver Disease

et al. 2017

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“…MPO, which was originally named verdoperoxidase due to its intense green colour, is a highly cationic, heme-containing, glycosylated enzyme [ 4 ] which is found mainly in primary (azurophilic) granules of neutrophils, making up approximately 5% of the total dry cell weight [ 5 ]. Human neutrophils contain about 5–10-fold higher levels of MPO than murine neutrophils [ 6 ]. MPO is also found, to a lesser extent, in monocytes where it constitutes about 1% of total cell protein [ 7 ].…”

Section: Biosynthesis Cellular Sources Storage and Release Of Mmentioning

confidence: 99%

Neutrophil-Mediated Regulation of Innate and Adaptive Immunity: The Role of Myeloperoxidase

Odobasic

Kitching

Holdsworth

2016

Journal of Immunology Research

156

118

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Neutrophils are no longer seen as leukocytes with a sole function of being the essential first responders in the removal of pathogens at sites of infection. Being armed with numerous pro- and anti-inflammatory mediators, these phagocytes can also contribute to the development of various autoimmune diseases and can positively or negatively regulate the generation of adaptive immune responses. In this review, we will discuss how myeloperoxidase, the most abundant neutrophil granule protein, plays a key role in the various functions of neutrophils in innate and adaptive immunity.

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“…Similarly, Rausch and Moore (13) have reported widely varying activities of this enzyme in the leukocytes of various species of animals, with rats possessing 1Ox and guinea pigs 40x the activity found in human cells. We recently examined the bactericidal activity of these three cells and observed an inverse relationship between LAP levels as reported by Rausch and Moore (13) and the functional capability of the cells (1). Finally, cells from a number of animal species, including rhesus monkeys and cats, have a natural deficiency in this enzyme (13); we are unaware of any data which suggest that these animals are more prone to bacterial infection than other species.…”

Section: Resultsmentioning

confidence: 73%

Dissociation of leukocyte alkaline phosphatase from the bactericidal activity of neutrophils

DeChatelet¹,

Shirley²,

McCall³

et al. 1979

Infect Immun

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We have identified an apparently healthy individual with no history of repeated infections whose neutrophils were virtually devoid ofalkaline phosphatase activity by either spectrophotometric or histochemical assay. His cells showed normal bactericidal activity toward both Staphylococcus aureus and Escherichia coli when tested in vitro. We have also demonstrated that L-p-bromolevamisole, a potent inhibitor of alkaline phosphatase in many tissues, is likewise an effective inhibitor of the neutrophilic enzyme. Concentrations of this compound which caused nearly complete inhibition of the neutrophilic enzyme did not impair the ability of intact cells to kill bacteria. These results suggest that leukocyte alkaline phosphatase is not required for the normal bactericidal activity of neutrophils.The enzyme alkaline phosphatase (orthophosphoric monoester phosphohydrolase, EC 3.1.3.1) is very nearly ubiquitous, yet its function remains obscure (4). There is some suggestion in the literature that the enzyme in human polymorphonuclear leukocytes is involved in the normal bactericidal activity of the cell. Strauss et al. (15) reported a patient with absent neutrophil alkaline phosphatase activity and a purported granule abnornality; the patient was subject to recurrent bacterial infections, and his cells demonstrated a slight impairment in bactericidal activity when tested in vitro. Similarly, Repine et al. (14) reported a patient with repeated infections associated with a primary deficiency in leukocyte alkaline phosphatase (LAP). Again, a marginal defect in in vitro bactericidal activity was reported. Finally, patients with infantile hypophosphatasia and a complete absence of LAP have been reported to suffer from severe bacterial infections (5); in vitro studies of leukocyte function, however, have not been performed on such patients to the best of our knowledge.In the present paper, we describe an apparently healthy individual with markedly abnormal LAP and normal bactericidal activity of his cells. We utilized a specific chemical inhibitor of LAP, L-p-bromolevamisole, and demonstrated a marked inhibition of the enzyme derived from normal cells with no effect on the bactericidal activity of the intact cells. These results suggest there is no necessary correlation between leukocytic function and the activity of LAP.MATERIALS AND METHODS Isolation of leukocytes. Leukocytes were isolated from normal human volunteers and from an individual with markedly decreased LAP. This patient, a white 30-year-old male with no past history of bacterial infection, remained completely asymptomatic over a 3-year period of study. His peripheral smear was normal upon repeated examination; he consistently maintained a normal absolute leukocyte count with a normal differential. The finding of reduced alkaline phosphatase activity was an incidental observation when he volunteered to serve as a source of control cells in an experiment; it was subsequently verified on numerous occasions by both biochemical and histochemical techniques. The patient ...

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Granule enzymes of polymorphonuclear neutrophils: A phylogenetic comparison

Cited by 174 publications

References 24 publications

Molecular MR Imaging of Myeloperoxidase Distinguishes Steatosis from Steatohepatitis in Nonalcoholic Fatty Liver Disease

Molecular MR Imaging of Myeloperoxidase Distinguishes Steatosis from Steatohepatitis in Nonalcoholic Fatty Liver Disease

Neutrophil-Mediated Regulation of Innate and Adaptive Immunity: The Role of Myeloperoxidase

Dissociation of leukocyte alkaline phosphatase from the bactericidal activity of neutrophils

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