Human myeloperoxidase gene: molecular cloning and expression in leukemic cells

Ks, Chang; Trujillo, JM; Cook, R G; Stass, SA

doi:10.1182/blood.v68.6.1411.bloodjournal6861411

Cited by 13 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Anti-MPO antibodies are found mainly in MPA, but also in several other autoimmune diseases. MPO, a haemoprotein predominantly present in azurophilic granules of polymorphonuclear leucocytes, plays a major role in the antimicrobicidal and cytotoxic activity of polymorphonuclear leucocytes by its ability to generate potent oxidant-chlorinated species [11]. It is a 120-150-kD dimer composed of one heavy (55-60 kD) and one light (14-15 kD) chain and carries two identical prosthetic haeme groups.…”

Section: Introductionmentioning

confidence: 99%

Anti-native and recombinant myeloperoxidase monoclonals and human autoantibodies

Audrain¹,

Baranger

Moguilevski

et al. 1997

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYMyeloperoxidase (MPO) is one of the main antigen targets of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic vasculitides. It has been suggested that anti-MPO antibodies may recognize a single epitope on recombinant MPO. If confirmed on native MPO, this might allow specific therapeutic intervention with anti-idiotypic MoAbs to prevent antibody-antigen interaction which is thought to cause activation of neutrophils and vasculitis. We searched for restriction in the epitope recognition profile in 50 patients with anti-MPO autoantibodies, using both native and recombinant MPO. Mouse monoclonals were purified and tested in competition assays. At least four epitopes were identified on native MPO using these monoclonals and only two were conserved on recombinant MPO. We found that human MPO autoantibody response was not restricted to a single epitope on native MPO, as all sera tested did not show the same profile in competitive studies with monoclonals. Furthermure, 30% of human anti-native MPO sera failed to recognize rMPO.

show abstract

Section: Introductionmentioning

confidence: 99%

Anti-native and recombinant myeloperoxidase monoclonals and human autoantibodies

Audrain¹,

Baranger

Moguilevski

et al. 1997

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Myeloperoxidase (MPO) is a heme containing glycoprotein synthesized at the promyelocytic stage of differentiation and present in the primary (azurophilic) granules of polymorphonuclear leukocytes (PMN) (Bainton et al, 1971). This enzyme reacts with HzOz and a halide ion as part of the microbicidal system of the PMN (Badwey and Karnovsky, 1980), and is involved in the modulation of inflammatory responses (Chang et al, 1986;Nauseef et al, 1983;Bainton et al, 1971). Myeloperoxidase is a basic protein with a MW of 140 kilodaltons (kD), composed of two heavy and two light chains of approximately 55 and 13.5 kD, respectively.…”

mentioning

confidence: 99%

“…Isolation of cDNA clones coding for MPO have recently been reported (Chang et al, 1986;Johnson et al, 1987;Morishita et al, 1987;Weil et al, 1987;Yamada et al, 1987). Both cDNA and intron specific probes of MPO have provided the tools for investigating aspects of MPO expression and regulation in normal and leukemic myeloid cells.…”

mentioning

confidence: 99%

Regulation of gene expression of myeloperoxidase during myeloid differentiation

Tobler

Miller

Johnson

et al. 1988

Journal Cellular Physiology

107

View full text Add to dashboard Cite

Myeloperoxidase (MPO) is a major heme enzyme involved in inflammatory responses of polymorphonuclear leukocytes. Using cDNA and intron specific probes for MPO we studied the regulation of MPO expression during myeloid differentiation of the promyelocytic HL-60 leukemia cell line. Mature MPO mRNA species of 3.3, 2.8 and 1.6 kb and heterogeneous nuclear (hn) RNA of greater than 8 and approximately 4 kb were observed in wildtype HL-60 cells. Induction of differentiation of the cells towards either granulocytes or macrophages resulted in a profound decrease (greater than 95%) in the concentration of MPO mRNA levels, showing that gene expression of MPO mRNA is closely linked to the stage of development of myeloid cells. Studies using normal and leukemic hematopoietic cells confirmed these findings and showed that myeloblasts and promyelocytes contain MPO mRNA. Rate of transcription of MPO was measured by a nuclear run-on assay in wild-type and day 3- and day -4 differentiated HL-60 cells and was nearly the same in all three. In contrast, rate of transcription of c-myc in the same nuclei became almost undetectable with induction of differentiation. Overall transcription decreased by 60% and 80% on day 3 and 4 of differentiation, respectively, compared to wild-type cells. Stability of mature MPO mRNA was also measured and found to be the same in wild-type and differentiated HL-60. Half-life of MPO hnRNA was less than or equal to 30 min in wild-type HL-60; nevertheless, this hnRNA was easily detectable 3 days after induction of differentiation of these cells. Taken together, the results show that decreased expression of MPO mRNA with differentiation occurs in part post-transcriptionally, possibly due to a failure in RNA processing. In addition, as overall transcription decreases during differentiation, MPO transcription is concomitantly reduced. This indicates that transcriptional and post-transcriptional mechanisms cooperate in the control of MPO gene expression.

show abstract

“…MPO is encoded by a single gene on chromosome 17q21-q22 (34). After cotranslational glycosylation, the 90-kDa apoproMPO acquires heme and undergoes posttranslational proteolytic processing to generate the lysosomal form of the enzyme, with subunits of 59-kDa and 14-kDa (6,10,11). Several studies have assigned to MPO deficiency an autosomal recessive pattern of inheritance (9,19,20,22), but the pattern appears to be more complex.…”

Section: Resultsmentioning

confidence: 99%

Prevalence of Inherited Myeloperoxidase Deficiency in Japan

Nunoi

Kohi

Kajiwara³

et al. 2003

Microbiology and Immunology

View full text Add to dashboard Cite

The microbicidal activity of the myeloperoxidase (MPO)-hydrogen peroxide-halide system has been implicated as the most efficient, oxygen-dependent antimicrobial component of neutrophil host defense. Unexpectedly, individuals with MPO deficiency suffer few clinical consequences. In order to understand better the clinical impact of MPO deficiency, we surveyed several clinical hematology laboratories in Japan to assess the prevalence of MPO deficiency in the general population. MPO activity was determined by flow cytometry using the Technicon H series of automated systems. We identified 26 cases of complete MPO deficiency, prevalence 1 in 57,135, and 129 cases of partial deficiency, prevalence 1 in 17,501. The distribution of complete and partial deficiencies differed among the laboratories studied.

show abstract

Human myeloperoxidase gene: molecular cloning and expression in leukemic cells

Cited by 13 publications

References 0 publications

Anti-native and recombinant myeloperoxidase monoclonals and human autoantibodies

Anti-native and recombinant myeloperoxidase monoclonals and human autoantibodies

Regulation of gene expression of myeloperoxidase during myeloid differentiation

Prevalence of Inherited Myeloperoxidase Deficiency in Japan

Contact Info

Product

Resources

About