Mast cells are important in the development of hypersensitivity pneumonitis. A study with mast-cell-deficient mice.
We have previously reported that C57B1/6 mice develop lung lesions similar to human hypersensitivity pneumonitis (HP) by repeated transnasal administration of Thermoactinomyces vulgaris antigen. Since the HP-like lesions were induced via respiratory route and by the causative antigen in human HP (farmer's lung), it seems that this murine model is useful for investigating the cell-to-cell interactions in human HP. To clarify the involvement of mast cells (MC) in the development of HP, T. vulgaris (90 micrograms/day) was transnasally administered to MC-deficient WBB6F1-W/Wv mice (W/Wv) and their littermates (+/+) five times a wk for 3 wk. When the lungs were examined by scoring pathological findings and lung indexes, HP-like lesions were significantly less severe in W/Wv than in +/+, whose lesions were equivalent to those of C57B1/6. Bone-marrow-derived cultured MC from +/+ mice (98% purity) were obtained by in vitro culture mixed with WEHI-3B-derived conditioned medium which contained IL-3. When these MC were adoptively transferred to W/Wv mice (10(7) cells/mouse), the HP-like lesions in W/Wv mice were enhanced to be as severe as those in +/+. Importantly, significant numbers of MC were found in the lungs of MC-transferred W/Wv mice. These results suggest that MC play an important role in the development of the murine experimental HP.
Takizawa
H
H
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Ohta
K
K
Hirai
K
K
Misaki
Y
Y
Horiuchi
T
T
Kobayashi
N
N
Shiga
J
J
Miyamoto
T
T
D000542:Alveolitis, Extrinsic Allergic / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D002452:Cell Count; D005260:Female; D006099:Granuloma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D006636:Histamine Release; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000235:genetics / Q000473:pathology; D007116:Immunization, Passive; D008168:Lung / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008848:Micromonosporaceae / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial