Document Detail


Relative contributions of human types 1 and 2 T-helper cell-derived eosinophilotrophic cytokines to development of eosinophilia.
MedLine Citation:
PMID:  8364199     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The relative contributions of type 1 and 2 T-helper (Th1 and Th2) cell-derived interleukin (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 were studied in the regulation of sequential events in the development of eosinophilia. Using eosinophils from normal donors and neutralizing antibodies that selectively block cytokine activities, we analyzed the effects of these cytokines in supernatants (SN) of well-characterized allergen-specific Th2 and Th1 T-lymphocyte clones (TLC) generated from atopic and nonatopic individuals, respectively. Eosinophil colony formation from CD34+ bone marrow progenitor cells in semisolid cultures could be induced both by Th1 and Th2 SN, mainly mediated by the synergistic effects of GM-CSF and IL-3, whereas IL-5 had only a minor additive effect. High production of mature eosinophils in liquid cultures of unseparated mononuclear bone marrow cells could only be induced by Th2 SN, which could be more than 90% blocked by anti-IL-5, but not by anti-IL-3 or anti-GM-CSF. Chemotaxis of mature peripheral blood eosinophils could equally well be induced by Th1 and Th2 SN, although the relative contribution of the individual cytokines was clearly different in the two sets of SN. Priming of platelet-activating factor (PAF) release by peripheral blood eosinophils was regulated by additive effects of the three cytokines and was stronger induced by the Th2 SN than by the Th1 SN. The present results indicate that IL-5, GM-CSF, and IL-3 control eosinophils throughout the course of development of eosinophilia, having different individual contributions in different compartments. The apparent strong and selective IL-5-dependence of certain yet undefined steps in eosinophil production in the bone marrow supports the concept of the generally assumed causal relation between predominant activation of IL-5-producing Th2 cells in response to allergens and development of eosinophilia in atopic disease.
Authors:
E A Wierenga; B Backx; M Snoek; L Koenderman; M L Kapsenberg
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood     Volume:  82     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1993 Sep 
Date Detail:
Created Date:  1993-10-05     Completed Date:  1993-10-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1471-9     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Cell Biology and Histology, University of Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Bone Marrow Cells
Chemotaxis, Leukocyte
Colony-Forming Units Assay
Cytokines / analysis,  metabolism*
Eosinophilia / etiology,  metabolism*
Eosinophils / cytology,  physiology
Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
Humans
Interleukin-3 / metabolism
Interleukin-5 / metabolism
Monocytes / metabolism
Platelet Activating Factor / secretion
Stem Cells / cytology
T-Lymphocytes, Helper-Inducer / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/Cytokines; 0/Interleukin-3; 0/Interleukin-5; 0/Platelet Activating Factor; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

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