The effect of cysteinyl leukotrienes on growth of eosinophil progenitors from peripheral blood and bone marrow of atopic subjects.
BACKGROUND
The accumulation of eosinophils into the peripheral blood and airways of asthmatic subjects is, in part, dependent on cysteinyl leukotrienes (cysLTs). However, the effect of cysLTs on peripheral blood and bone marrow eosinophil pro-genitor cells in allergic subjects is not known.


OBJECTIVE
The purpose of this study was to evaluate the effects of leukotriene (LT) D(4) and LTE(4) and the cysLT(1) receptor antagonist montelukast on peripheral blood and bone marrow eosinophil-basophil progenitor growth and development in atopic subjects.


METHODS
Semisolid methylcellulose cultures for peripheral blood and bone marrow eosinophil-basophil colonies were counted after incubation with or without addition of LTD(4), LTE(4), and montelukast in the presence of suboptimal concentrations of GM-CSF, IL-3, and IL-5.


RESULTS
Peripheral blood eosinophil-basophil colony-forming unit cultures grown in the presence of GM-CSF and bone marrow eosinophil-basophil colony-forming units grown in the presence of IL-5 were significantly increased by the addition of LTD(4) (0.1 micromol/L). This increase was suppressed by montelukast (1 micromol/L).


CONCLUSIONS
This study has demonstrated that the cysLT LTD(4) can stimulate proliferation of eosinophil hematopoietic progenitor cells in the presence of eosinophilopoietic cytokines. The suppressive effect by montelukast demonstrates that this is a cysLT(1) receptor-mediated effect.
Asthma Research Group, Firestone Institute for Respiratory Health, St Joseph's Healthcare, and the Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Fausto
F
Braccioni
Sandra C
SC
Dorman
Paul M
PM
O'byrne
Mark D
MD
Inman
Judah A
JA
Denburg
Krishnan
K
Parameswaran
Adrian J
AJ
Baatjes
Ronan
R
Foley
Gail M
GM
Gauvreau
D000085:Acetates / Q000494:pharmacology; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood*; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology*; D017999:Leukotriene E4 / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D017998:Leukotriene D4; D017999:Leukotriene E4; C093875:montelukast