Chemokines of the ⍺, β-subclass inhibit human basophils' responsiveness to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 - 12/09/11
Abstract |
Monocyte chemotactic and activating factor (MCAF) is the most potent cytokine that activates basophils to release histamine. The response of human basophils to either simultaneous or sequential addition of the chemokines RANTES, macrophage inflammatory protein (MIP)-1⍺, MIP-1β, platelet factor (PF)4, connective tissue activating peptide III (CTAP-III), interleukin (IL)-8, and inflammatory protein (IP)-10 on MCAF-induced histamine release was studied. Simultaneous addition of MCAF and any of the chemokines studied evoked an augmented response as measured by histamine release, whereas preincubation of leukocytes or purified basophils (80%) with these chemokines decreased MCAF-induced histamine release in a dose-dependent manner. Histamine release by anti-IgE remained unchanged. When tested at 5 × 10-9 mol/L, the decrease in histamine release by RANTES was 69.2% ± 3.5%, by MIP-1⍺ 48.8% ± 3.1%, by MIP-1β 42.9% ± 3.1%, by PF4 56.5% ± 2.9%, by IL-8 41.2% ± 2.2, by CTAP III 27% ± 4.4%, and by IP-10 15.3% ± 2.6%. The peak inhibition of histamine release by the chemokines was reached within 10 minutes of preincubation with basophils and remained unchanged thereafter. Washing basophils after preincubation with chemokines abolished the inhibition, with the exception of desensitization by low concentrations of MCAF. With the exclusion of MCAF and RANTES, none of the chemokines (at the concentration range of 5 × 10-8 to 5 × 10-11) induced significant (>10% above spontaneous) histamine release from basophils. Preincubation of basophils with C5a (5 × 10-10 mol/L) did not affect histamine release, whereas preincubation with granulocyte-macrophage colony-stimulating factor (10 ng/ml) or IL-5 (10 ng/ml) enhanced MCAF-induced histamine release by 121.8% ± 10.1% and 108% ± 10.8%, respectively. We have therefore characterized RANTES, MIP-1⍺, MIP-1β, CTAP III, PF4, IL-8, and IP-10 as inhibitors of MCAF-induced histamine release. Although the results are consistent with receptor blockade, the ⍺ and β chemokines appear to interact with separate receptors linked to G proteins; thus, a mechanism of receptor class desensitization is proposed. Interaction of this group of cytokines at the site of allergic inflammation may modulate a function of basophils to initiate, augment, or inhibit histamine release. (J ALLERGY CLIN IMMUNOL 1995;95:574-86.)
Le texte complet de cet article est disponible en PDF.Keywords : Chemokines, cytokines, histamine release, basophils
Abbreviations : CTAP-III, D-PBS, D-PBS-BSA, GM-CSF, HBS, HRF, HRIF, HSA, IL, IP-10, MCAF, MCP, MIP, NAP-2, PF4, RANTES
Plan
From athe Division of Allergy, Rheumatology and Clinical Immunology, Department of Medicine, State University of New York-Stony Brook, Health Sciences Center; and bGenentech, Inc., San Francisco. |
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Reprint requests: Allen P Kaplan, MD, Department of Medicine, SUNY-Stony Brook, HSC T-16, Stony Brook, NY 11794-8160. |
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0091-6749/95 $3.00 + 0 1/1/60290 |
Vol 95 - N° 2
P. 574-586 - février 1995 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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