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Monocytes, but not macrophages, produce the eosinophil cationic protein
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2001 (English)In: APMIS: Acta pathologica, microbiologica et immunologica Scandinavica. Supplementum, ISSN 0903-465X, Vol. 109, no 7-8, 507-516 p.Article in journal (Refereed) Published
Abstract [en]

The eosinophil cationic protein (ECP) is a cytotoxic protein with ribonuclease activity, produced and stored in bone marrow eosinophil myelocytes. Mature circulating eosinophils contain about 10 pg ECP per cell. The aim of this study was to investigate the possibility that monocytes produce and store ECP. By results from flow cytometry and specific protein measurement it is shown that human monocytes contain ECP (monocytes about 10 fg ECP per cell). RT-PCR analysis indicated the presence of mRNA coding for ECP in blood monocytes but not in alveolar macrophages. Furthermore, mRNA coding for ECP and low amounts of the protein were found in three myeloid cell lines representing different stages of monocytic differentiation. Differentiation of U-937 cells to macrophages induced lowered transcription of the ECP gene and reduced protein production. Immunohistochemical staining of lung tissue indicated that lung macrophages do not contain ECP. It is concluded that ECP is produced to a low extent by human monocytes and that the production is shut down during macrophage differentiation. This might indicate an alternative transcriptional regulation of the ECP gene in the monocytic lineage compared to the eosinophil lineage.

Place, publisher, year, edition, pages
2001. Vol. 109, no 7-8, 507-516 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-89877DOI: 10.1111/j.1600-0463.2001.907804.xPubMedID: 11552948OAI: oai:DiVA.org:uu-89877DiVA: diva2:161706
Available from: 2002-05-08 Created: 2002-05-08 Last updated: 2009-12-18Bibliographically approved
In thesis
1. Eosinophil Cationic Protein : Expression Levels and Polymorphisms
Open this publication in new window or tab >>Eosinophil Cationic Protein : Expression Levels and Polymorphisms
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The eosinophil cationic protein (ECP) is usually associated with the eosinophil granulocyte. In this thesis the presence and production of this protein has been studied in two other cells. The circulating monocyte was found to contain ECP mRNA and small amounts of ECP, one thousand times less than that found in the eosinophil. The production decreased by differentiation of the myelomonoblastic cell line U937 into a macrophage phenotype. Submucosal lung macrophages did not stain for ECP and alveolar macrophages did not contain ECP mRNA. The circulating neutrophil contains ECP at a level hundred fold less than the eosinophil. We found that the protein is located to the primary granules of the neutrophil but could detect no ECP mRNA in the cell. It was shown in vitro that the protein was taken up by the cell and partly transported to the primary granules. The uptake did not seem to be receptor mediated. Upon stimulation of the neutrophils, ECP previously taken up, was re-secreted.

The ECP protein is heterogeneous both to molecular characteristics and to function. To evaluate if a genetic component is involved, the ECP gene was analysed in 70 individuals. Three single nucleotide polymorphisms (SNP´s) were found, denoted 277(C>T), 434(G>C) and 562(G>C). The two first were located to the mature peptide-coding region and would change the amino acids, arg45cys and arg97thr. The prevalence of the most common SNP, 434, was evaluated in two eosinophil-related diseases, allergy/asthma and Hodgkin Lymphoma (HL). Forty-three HL patients were evaluated and it was found that the 434GG was significantly more prevalent in patients having nodular sclerosis (NS) as compared to other histologies (p=0.03). Erythrocyte sedimentation rate was also related to the 434GG genotype (p=0.009). In 209 medical students 434GG was more common (p=0.002) in those who indicated allergy. The genotype was unrelated to the production of IgE antibodies to allergens. In analysis of 76 subjects with asthma it was found that the 434GG genotype was significantly more common among allergic asthmatics (p=0.04). Asthma and HL-NS are characterized by fibrosis and eosinophils and ECP has been suggested in fibrosis development.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 58 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1161
Keyword
Medical sciences, Eosinophils, Neutrophils, Monocytes, Macrophages, mRNA, eosinophil cationic protein, DNA, polymorphism, Hodgkin Lymphoma, asthma, allergy, MEDICIN OCH VÅRD
National Category
Medical and Health Sciences
Research subject
Clinical Chemistry
Identifiers
urn:nbn:se:uu:diva-2059 (URN)91-554-5336-8 (ISBN)
Public defence
2002-05-29, Rosénsalen, Uppsala, 13:15
Opponent
Available from: 2002-05-08 Created: 2002-05-08Bibliographically approved

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