TY - JOUR
T1 - Expression of functional cysteinyl leukotriene receptors by human basophils
AU - Gauvreau, Gail M.
AU - Plitt, Jim R.
AU - Baatjes, Adrian
AU - MacGlashan, Donald W.
N1 - Funding Information:
Dr Gauvreau received funding from the Canadian Institute of Health Research.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/7
Y1 - 2005/7
N2 - Background: Synthesis of leukotriene (LT) C4 by basophils and mast cells is an important component of IgE-mediated inflammation, resulting in increased levels of the cysteinyl leukotrienes (cysLTs) LTC4, LTD4, and LTE4. Receptors for cysLTs are expressed on a variety of peripheral blood leukocytes, but of interest, they are also expressed on cells that synthesize LTC4, such as eosinophils and mast cells. Objective: We examined human basophils for expression and function of cysLT receptor type 1 (cysLT1) and cysLT receptor type 2 (cysLT2). Methods: Basophils were purified from human blood and analyzed by means of RT-PCR, Western blotting, and flow cytometry for receptor expression. Basophils were also examined for functional responses to LTD4, including cytosolic calcium flux, histamine release, viability, and chemotaxis. Results: We found that basophils express mRNA for cysLT1 and cysLT2. CysLT1 and cysLT2 were also detectable by means of flow cytometry, but only cysLT2 was detectable by means of Western blotting with available antibodies. Increases in cytosolic calcium induced by LTD4-stimulated basophils were inhibited by the cysLT1 receptor antagonist zafirlukast, confirming the presence of functional cysLT1 receptors on basophils. There was no significant effect of LTD4 on histamine release; however, LTD4 decreased CD95 (Fas) expression on basophils in several-day cultures. Conclusions: We have demonstrated that basophils express the cysLT receptors cysLT1 and cysLT2, and some functional responses to LTD4 can be observed.
AB - Background: Synthesis of leukotriene (LT) C4 by basophils and mast cells is an important component of IgE-mediated inflammation, resulting in increased levels of the cysteinyl leukotrienes (cysLTs) LTC4, LTD4, and LTE4. Receptors for cysLTs are expressed on a variety of peripheral blood leukocytes, but of interest, they are also expressed on cells that synthesize LTC4, such as eosinophils and mast cells. Objective: We examined human basophils for expression and function of cysLT receptor type 1 (cysLT1) and cysLT receptor type 2 (cysLT2). Methods: Basophils were purified from human blood and analyzed by means of RT-PCR, Western blotting, and flow cytometry for receptor expression. Basophils were also examined for functional responses to LTD4, including cytosolic calcium flux, histamine release, viability, and chemotaxis. Results: We found that basophils express mRNA for cysLT1 and cysLT2. CysLT1 and cysLT2 were also detectable by means of flow cytometry, but only cysLT2 was detectable by means of Western blotting with available antibodies. Increases in cytosolic calcium induced by LTD4-stimulated basophils were inhibited by the cysLT1 receptor antagonist zafirlukast, confirming the presence of functional cysLT1 receptors on basophils. There was no significant effect of LTD4 on histamine release; however, LTD4 decreased CD95 (Fas) expression on basophils in several-day cultures. Conclusions: We have demonstrated that basophils express the cysLT receptors cysLT1 and cysLT2, and some functional responses to LTD4 can be observed.
KW - Basophil
KW - Chemotaxis
KW - Cysteinyl leukotriene receptor type 1
KW - Cysteinyl leukotriene receptor type 2
KW - Viability
KW - mRNA
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U2 - 10.1016/j.jaci.2005.03.014
DO - 10.1016/j.jaci.2005.03.014
M3 - Article
C2 - 15990778
AN - SCOPUS:21344451873
SN - 0091-6749
VL - 116
SP - 80
EP - 87
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -