Die Alius-Grignaschi-Anomalie: Der erblich-konstitutionelle Peroxydasedefekt der Neutrophilen und Monozyten

Undritz, E

doi:10.1007/bf01631534

Cited by 60 publications

(22 citation statements)

References 2 publications

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“…The ability of our patient to escape significant bacterial infection for over four decades, the continued well being of his sister and the reported good health of the three previously described subjects with MPO deficiency (17,18) seem incompatible with suggestions that MPO is the major mediator of neutrophil bactericidal function in man. Our patient's MPO-deficient cells killed S. aureus 502A and S. inarcescens at distinctly subnormal rates; however, killing of the ingested bacteria eventually approached completion.6 These observations indicate the presence of alternative bactericidal mechanisms effective in the absence of MPO and suggest that 'Lehrer, R. I., J. Hanifin, and M. J. Cline.…”

Section: Functional Studiescontrasting

confidence: 77%

“…This pattern of peroxidase deficiency has been reported previously in only three subjects, otherwise normal, two of whom were brother and sister (17,18). Morphologic, biochemical, and functional studies on the leukocytes of the patient and available family members confirmed the genetic nature of the defect, clarified its mode of transmission, and allowed appraisal of some of the suggested biochemical and functional contributions of MPO to the intracellular economy of the neutrophil.…”

Section: Introductionsupporting

confidence: 79%

“…In recent immunologic and spectrophotometric investigations,5 we found normal EPO and MIPO to be immunologically distinct and demonstrated that our patient's neutrophils also lack MPO detectable by these analytic techniques. The family studies reported here, as well as histochemical observation in family members of the three subjects with hereditary MPO deficiency (17,18), support an autosomal recessive mode of transmission for this condition.…”

Section: Functional Studiessupporting

confidence: 73%

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Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection

Lehrer¹,

Cline²

1969

J. Clin. Invest.

666

278

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A B S T R A C T The neutrophils and monocytes of a patient with disseminated candidiasis were found to lack detectable levels of the lysosomal enzyme myeloperoxidase (MPO), although they had normal levels of other granule-associated enzymes. Leukocytes from one of the patient's sisters also lacked detectable MPO; leukocytes from his four sons contained approximately one-third of mean normal peroxidase levels. Neither the patient nor his affected relatives had experienced frequent or unusual bacterial infections.The phagocytic activity of the patient's MPO-deficient neutrophils was intact, and the cells displayed normal morphologic and metabolic responses to phagocytosis. In contrast to normal leukocytes which killed 30.5 ±7.3% of ingested Candida albicans in 1 hr, however, the patient's neutrophils killed virtually none. His leukocytes also failed to kill the strain of C. albicans recovered from his lesions, as well as other Candida. species. These MPO-deficient neutrophils killed Serratia marcescens and Staphylococcus aureus 502A at an abnormally slow rate, requiring 3-4 hr to achieve the bactericidal effect attained by normal leukocytes after 45 min. No other abnormalities in his cellular or humoral immune responses were demonstrated.These findings suggest that hereditary MPO deficiency is transmitted as an autosomal recessive characteristic, that the homozygous state conveys enhanced susceptibility to disseminated candidiasis, and that MPO is necessary for candidacidal activity in human neutrophils.This work was presented in part at the National Meeting of the American Federation for Clinical Research, Atlantic City, N. J., and published in abstract form (1).

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Section: Functional Studiescontrasting

confidence: 77%

Section: Introductionsupporting

confidence: 79%

Section: Functional Studiessupporting

confidence: 73%

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Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection

Lehrer¹,

Cline²

1969

J. Clin. Invest.

666

278

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“…Hereditary MPO deficiency is a rare condition in which MPO is absent from neutrophils and monocytes (34,35,26). Patients with this condition have leukocytes with decreased fungicidal and bactericidal activity (26,36,37 Phagocytosing leukocytes from one patient with this condition degraded T4 and T3 at a slower rate than did normal leukocytes (Fig.…”

Section: Chronic Granulomatous Disease Patients With Cgdmentioning

confidence: 99%

Degradation of Thyroid Hormones by Phagocytosing Human Leukocytes

Klebanoff¹,

Green²

1973

J. Clin. Invest.

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A B S T R A CT Thyroxine (T4) and triiodothyronine (T3) are rapidly degraded by a purified preparation of myeloperoxidase (MPO) and H202 with the formation of iodide and material which remains at the origin on paper chromatography. Deiodination by MPO and H202 occurs more readily at pH 7.0 than at pH 5.0 in contrast to iodination by this system which is known to occur more readily at pH 5.0 than at pH 7.0. Degradation is inhibited by azide, cyanide, ascorbic acid, and propylthiouracil. Methimazole stimulates deiodination by MI PO and H202 but inhibits this reaction when MIPO is replaced by lactoperoxidase or horseradish peroxidase.Intact human leukocytes, in the resting state, degrade T4 and T3 slowly; degradation, however, is increased markedly during phagocytosis of preopsonized particles. Serum inhibits this reaction. T3 can be detected as a minor product of T4 degradation. Proteolytic digestion of the reaction products increases the recovery of monoiodotyrosine. The fixation of iodine in the cytoplasm of leukocytes which contain ingested bacteria was detected radioautographically. Chronic granulomatous disease leukocytes, which are deficient in H202 formation, degrade T4 and T3 poorly during phagocytosis. MPO-deficient leukocytes degrade the thyroid hormones at a slower rate than do normal leukocytes although considerable degradation is still observed. Azide, cyanide, ascorbic acid, and propylthiouracil which inhibit certain peroxidasecatalyzed reactions inhibit degradation by normal leukocytes; however, inhibition is incomplete. Formation of iodinated origin material is inhibited to a greater degree by azide, cyanide, and propylthiouracil than is deiodination. Methimazole inhibits the formation of iodinated origin material by both normal and MPO-deficient leukoThese studies were presented in part at the 64th These data suggest that both MPO-dependent and MPO-independent systems are involved in the degradation of T4 and T3 by phagocytosing leukocytes. The role of leukocytic degradation of T4 and T3 in thyroid hormone economy and in leukocytic microbicidal activity is considered.

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“…The myeloperoxidase (MPO)-hydrogen peroxide-halogen system is deemed an important bactericidal mechanism of polymorphonuclear leukocytes (PMN) (1). However, in a few reported cases, individuals have been found to have PMN deficient in MPO although they are healthy and free of bacterial infections (2,3). Previous investigations by one of the authors has established that the PMN of chickens are naturally devoid of MPO although they are quite capable of lethal activity against a variety of microorganisms (4,5).…”

mentioning

confidence: 99%

Chicken neutrophils: oxidative metabolism in phagocytic cells devoid of myeloperoxidase.

Penniall¹,

Spitznagel²

1975

Proc. Natl. Acad. Sci. U.S.A.

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Polymorphonuclear leukocytes isolated from chicken peritoneal exudates have been found to catalyze cyanide-insensitive stimulation of respiration and the hexose monophosphate shunt upon exposure to heat-inactivated Staphylococcus aureus. However, there was no demonstrable formate oxidation concomitant with phagocytosis in either the presence or absence of exogenous catalase. Moreover, chicken polymorphonuclear leukocytes failed to oxidize scopoletin concomitant with phagocytosis in the presence of horseradish peroxidase. While oxygen uptake was increased 2-to 3fold by the stimulus of phagocytosis, the oxidation of [1-'4Clglucose was increased approximately 20-fold. The cells contain two mechanisms, a glutathione reductase-glutathione peroxidase system and an NADPH-NAD+ transhydrogenase, each of which is present in sufficient capacity to accommodate the enhanced shunt activity. Although chicken polymorphonuclear leukocytes were found to possess a substantial capacity to catalyze the cyanide-insensitive oxidation of either NADH or NADPH, the total or specific activities of such processes were not demonstrably affected by phagocytosis. The myeloperoxidase (MPO)-hydrogen peroxide-halogen system is deemed an important bactericidal mechanism of polymorphonuclear leukocytes (PMN) (1). However, in a few reported cases, individuals have been found to have PMN deficient in MPO although they are healthy and free of bacterial infections (2, 3). Previous investigations by one of the authors has established that the PMN of chickens are naturally devoid of MPO although they are quite capable of lethal activity against a variety of microorganisms (4, 5). As potential bactericidal mechanisms, the chicken PMN contain a family of six low-molecular-weight cationic proteins and two structurally distinct lysozymes (6). Because it is devoid of MPO, we have considered the possibility that chicken PMN provide a naturally occurring counterpart of the MPO-deficient PMN of humans. In order to further explore this possibility, we have evaluated certain of the parameters of oxidative metabolism in chicken PMN. Such a study might pinpoint fundamental similarities or differences in the biochemical characteristics of the PMN of chickens and humans, thereby adding to an increased understanding of the bactericidal mechanisms of both cell types. EXPERIMENTAL Chicken PMN were elicited and harvested from the peritoneal cavity in essentially the same fashion and purity as described previously (4, 5 to the incubation system at a level of 105 cpm per flask; the specific activities were 45, 53.7, and 24.5 mCi/mmol, respectively. H'4COONa was prepared for use by acidification and evacuation (followed by subsequent neutralization) to remove any contaminating 14CO2. Evolved '4CG2 was collected on Fiberglas paper containing 0.2 ml of 20% KOH, and the radioactivity was determined in a toluene-Triton

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Die Alius-Grignaschi-Anomalie: Der erblich-konstitutionelle Peroxydasedefekt der Neutrophilen und Monozyten

Cited by 60 publications

References 2 publications

Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection

Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection

Degradation of Thyroid Hormones by Phagocytosing Human Leukocytes

Chicken neutrophils: oxidative metabolism in phagocytic cells devoid of myeloperoxidase.

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