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The chemokine receptor CXCR4 is expressed within the mast cell lineage and its ligand stromal cell-derived factor-1alpha acts as a mast cell chemotaxin
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
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2000 In: European Journal of Immunology, Vol. 30, no 12, 3614-3622 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2000. Vol. 30, no 12, 3614-3622 p.
Identifiers
URN: urn:nbn:se:uu:diva-90100OAI: oai:DiVA.org:uu-90100DiVA: diva2:162297
Available from: 2003-01-22 Created: 2003-01-22Bibliographically approved
In thesis
1. The Role of Chemokines in Mast Cell Migration
Open this publication in new window or tab >>The Role of Chemokines in Mast Cell Migration
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mast cells are very potent multifunctional effector cells of the immune system normally distributed throughout connective tissues. An accumulation of mast cells has been described in several pathological conditions such as allergic- and autoimmune inflammations and in certain tumours. This necessitates two different processes: 1) Recruitment of mast cell progenitors from peripheral blood; 2) Accretion of mature mast cells at sites of inflammation and tumour areas. Both processes are depending on the local production of chemotactic factors. The aim of this study was to investigate the role of chemokines and their corresponding receptors in mast cell chemotaxis.

By cloning and mRNA-screening of cord blood derived mast cells several chemokine receptors were found to be expressed. Functional expression was confirmed of chemokine receptors CXCR4, CCR1 and CCR4. CXCL12, the only known ligand for CXCR4, acted as a mast cell chemotaxin and induced migration of progenitor cells with capacity to differentiate into mast cells. Of several ligands known to bind CCR1 and CCR4, only CCL5 induced migration of mast cells. The migration to CCL5 was mediated through both CCR1 and CCR4. In contrast, the ligands to CCR4, CCL17 and CCL22, could inhibit CCL5-induced migration. Expression of CCR1 and CCR4 could also be confirmed on mast cells in lung from asthmatic patients. Furthermore, we could demonstrate that mast cells were attracted by CCL5 produced by tumour cells in Hodgkin´s lymphoma.

In conclusion, the work in this thesis has identified two chemokines that regulates mast cell migration. This knowledge helps us understand the mechanisms behind homing of mast cell progenitors from the blood into the tissue and the accumulation of mature mast cells at sites of inflammation and tumourigenesis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 68 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1219
Keyword
Pathology, Mast cells, chemotaxis, calcium flux, chemokines and chemokine receptors, Patologi
National Category
Cell and Molecular Biology
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-3273 (URN)91-554-5508-5 (ISBN)
Public defence
2003-02-14, Rudbecksalen, Rudbecklaboratoriet, Uppsala, 09:15
Opponent
Available from: 2003-01-22 Created: 2003-01-22Bibliographically approved

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