Evidence for a pretranslational defect in hereditary and acquired myeloperoxidase deficiency

A. Tobler, M. E. Selsted, C. W. Miller, Keith R Johnson, M. J. Novotny, G. Rovera, H. P. Koeffler

Research output: Contribution to journalArticle

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Abstract

Myeloperoxidase (MPO) is a heme containing enzyme involved in the oxygen-dependent microbicidal activity of human polymorphonuclear leukocytes (PMN). Complete hereditary and acquired MPO deficiencies are defined as lack of peroxidase activity in PMN. Using this criterion, we studied a patient with complete hereditary MPO deficiency, and a MPO deficient variant cell line of HL-60 (HL-60-A7), which we used as a model for acquired MPO deficiency. Western blot analysis showed complete absence of mature and precursor protein of MPO both in PMN from the patient and in HL-60-A7 cells. PMN from both parents had one half of normal levels of these proteins. To study further the molecular basis of this defect, we isolated an intron specific probe for MPO and used it and a cDNA probe. Both normal human bone marrow cells and the promyelocytic HL-60 leukemia cells contained MPO mRNA species of 2.8, 3.3, ≃4, and >8 kilobase (kb). The transcripts of >8 and ≃4 kb contained sequences hybridizing to a probe specific for intron 7 of the MPO gene. Bone marrow cells of the MPO deficient patient contained two species of heterogenous nuclear (hn) RNA of >8 and ≃4 kb, but only trace amounts of the normal sized 3.3 kb MPO mRNA and undetectable 2.8 kb MPO mRNA. HL-60-A7 cells contained both >8 and ≃4 kb hnRNA, but only small amounts of normal sized 2.8 kb MPO mRNA and undetectable levels of the 3.3 kb mRNA. Southern blot analyses revealed no gross alteration of the MPO gene in both cases. Our results suggest that a pretranslational defect is one mechanism leading to MPO deficiency.

Original languageEnglish (US)
Pages (from-to)1980-1986
Number of pages7
JournalBlood
Volume73
Issue number7
StatePublished - Jan 1 1989

Fingerprint

Peroxidase
Defects
HL-60 Cells
Neutrophils
Messenger RNA
Bone Marrow Cells
Introns
Myeloperoxidase Deficiency
Cells
Nuclear RNA
Bone
Protein Precursors
Genes
Southern Blotting
Heme
Human Activities
Leukemia
Complementary DNA
Parents
Western Blotting

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Tobler, A., Selsted, M. E., Miller, C. W., Johnson, K. R., Novotny, M. J., Rovera, G., & Koeffler, H. P. (1989). Evidence for a pretranslational defect in hereditary and acquired myeloperoxidase deficiency. Blood, 73(7), 1980-1986.

Evidence for a pretranslational defect in hereditary and acquired myeloperoxidase deficiency. / Tobler, A.; Selsted, M. E.; Miller, C. W.; Johnson, Keith R; Novotny, M. J.; Rovera, G.; Koeffler, H. P.

In: Blood, Vol. 73, No. 7, 01.01.1989, p. 1980-1986.

Research output: Contribution to journalArticle

Tobler, A, Selsted, ME, Miller, CW, Johnson, KR, Novotny, MJ, Rovera, G & Koeffler, HP 1989, 'Evidence for a pretranslational defect in hereditary and acquired myeloperoxidase deficiency', Blood, vol. 73, no. 7, pp. 1980-1986.
Tobler A, Selsted ME, Miller CW, Johnson KR, Novotny MJ, Rovera G et al. Evidence for a pretranslational defect in hereditary and acquired myeloperoxidase deficiency. Blood. 1989 Jan 1;73(7):1980-1986.
Tobler, A. ; Selsted, M. E. ; Miller, C. W. ; Johnson, Keith R ; Novotny, M. J. ; Rovera, G. ; Koeffler, H. P. / Evidence for a pretranslational defect in hereditary and acquired myeloperoxidase deficiency. In: Blood. 1989 ; Vol. 73, No. 7. pp. 1980-1986.
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