Evaluation of cysteinyl leukotriene-induced contraction of human cultured bronchial smooth muscle cells.
BACKGROUND
Cysteinyl leukotrienes (cysLTs) are major mediators involved in bronchial asthma, particularly bronchial constriction. However, a contractile response of human bronchial smooth muscle cells (hBSMCs) to cysLTs has not been well characterized at cellular level.


METHODS
A contraction assay using collagen gel embedded with cultured hBSMCs was established to analyze contractile responses at cellular level. Contractile responses to several constrictors including cysLTs were evaluated in 6-day cultured gels with varying fetal bovine serum (FBS) concentrations.


RESULTS
Removal of FBS from the culture for the designated time periods resulted in increased contractile responses. CysLT-induced contraction of the gel became more pronounced and reproducible. CysLT(1)R expression on the hBSMCs was significantly increased by the removal of FBS.


CONCLUSIONS
Contractile responses of hBSMCs to cysLTs can be evaluated at cellular level for the first time. This experimental system may be useful for the in vitro evaluation and future development of cysLTs antagonists.
Kitamura
Noriko
N
National Hospital Organization, Sagamihara National Hospital, Clinical Research Center for Allergy and Rheumatology, Sagamihara 228-8522, Japan.
Kaminuma
Osamu
O
Ohtomo
Takayuki
T
Kiyokawa
Nobutaka
N
Kobayashi
Noriaki
N
Suko
Matsunobu
M
Mori
Akio
A
D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism* / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D018077:Receptors, Leukotriene / Q000096:biosynthesis
D007155:Immunologic Factors; D015289:Leukotrienes; D018077:Receptors, Leukotriene; C112381:cysteinyl-leukotriene; D003545:Cysteine; C083169:leukotriene D4 receptor