Comparative study to elucidate the mechanism underlying the difference in airway hyperresponsiveness between two mouse strains.
The mechanism underlying airway hyperresponsiveness (AHR), a characteristic feature of asthma, remains obscure. We attempted to elucidate the mechanism responsible for the different degrees of AHR in two mouse strains, BALB/c and C57BL/6, following exposure to an anaphylactic trigger. When ovalbumin (OVA)-sensitized mice were challenged daily with OVA for up to three consecutive days, the BALB/c mice showed a higher degree of airway responsiveness to methacholine than did C57BL/6. Following the OVA challenge, eosinophils and macrophages in bronchoalveolar lavage fluid (BALF) from BALB/c increased significantly in number compared to those from C57BL/6. BALB/c mice also exhibited a higher serum IgE level than that of C57BL/6 after OVA challenge. The enhanced AHR and eosinophilic infiltration in BALF were significantly reduced by pretreatment with a selective cysteinyl-leukotriene type 1 receptor (cysLT(1)R) antagonist, montelukast. In the in vitro study, cysLT production was significantly lower in the dissected lung tissue from BALB/c than in tissue from C57BL/6 when both groups were stimulated with saline. The lungs from BALB/c generated significantly larger amounts of cysLTs on incubation with OVA rather than with saline, while the lungs from C57BL/6 did not show any significant increase in cysLTs with antigen stimulation. Significant upregulation of cysLT(1)R and cysLT(2)R mRNA expression was induced by OVA challenge in the lungs of BALB/c, but not in those of C57BL/6. It is suggested that, after an anaphylactic reaction, the degree of AHR is dependent on the genetic background and that cysLTs play an important role in the mechanism involved.
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Juri
J
Fukunaga
Masayoshi
M
Abe
Akira
A
Murai
Yoshiharu
Y
Akitake
Masato
M
Hosokawa
Mitsuo
M
Takahashi
D000085:Acetates / Q000494:pharmacology; D000280:Administration, Inhalation; D000818:Animals; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003521:Cyclopropanes; D003545:Cysteine / Q000032:analysis / Q000096:biosynthesis; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D020024:Leukotriene Antagonists / Q000494:pharmacology; D015289:Leukotrienes / Q000032:analysis / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics / Q000276:immunology*; D008810:Mice, Inbred C57BL / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011804:Quinolines / Q000494:pharmacology; D018077:Receptors, Leukotriene / Q000032:analysis / Q000096:biosynthesis; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D007074:Immunoglobulin G; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; C112381:cysteinyl-leukotriene; D016210:Methacholine Chloride; D010047:Ovalbumin; D003545:Cysteine; C093875:montelukast