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.
Fukunaga
Juri
J
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Abe
Masayoshi
M
Murai
Akira
A
Akitake
Yoshiharu
Y
Hosokawa
Masato
M
Takahashi
Mitsuo
M
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