Expression of functional cysteinyl leukotriene receptors by human basophils.
BACKGROUND
Synthesis of leukotriene (LT) C 4 by basophils and mast cells is an important component of IgE-mediated inflammation, resulting in increased levels of the cysteinyl leukotrienes (cysLTs) LTC 4 , LTD 4 , and LTE 4 . Receptors for cysLTs are expressed on a variety of peripheral blood leukocytes, but of interest, they are also expressed on cells that synthesize LTC 4 , 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 LTD 4 , 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 LTD 4 -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 LTD 4 on histamine release; however, LTD 4 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 LTD 4 can be observed.
Department of Medicine, McMaster University, Hamilton, MD, USA.
Gail M
GM
Gauvreau
Jim R
JR
Plitt
Adrian
A
Baatjes
Donald W
DW
MacGlashan
D001491:Basophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006632:Histamine / Q000096:biosynthesis; D006801:Humans; D007211:Indoles; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017998:Leukotriene D4 / Q000276:immunology / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis*; D048448:Phenylcarbamates; D018077:Receptors, Leukotriene / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000494:pharmacology; D019014:fas Receptor / Q000187:drug effects / Q000276:immunology
D007211:Indoles; D018793:Interleukin-13; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D048448:Phenylcarbamates; D018077:Receptors, Leukotriene; D013449:Sulfonamides; D014105:Tosyl Compounds; D019014:fas Receptor; D015847:Interleukin-4; D017998:Leukotriene D4; D006632:Histamine; C083169:leukotriene D4 receptor; D002118:Calcium; C062735:zafirlukast