Activation of connective tissue-type and mucosal-type mast cells in compound 48/80-induced airway response.
The pathology of non-immunological airway contraction is not well understood. To define the activation of different phenotypes of mast cells, a rat non-immunological asthmatic model was prepared. Airway contraction in rats was measured by an unrestrained whole-body plethysmographic system following a 10-min inhalation challenge with a 5% solution of compound 48/80. Histamine, leukotrein C(4) (LTC(4)) and tumor necrosis factor (TNF)-alpha levels in bronchoalveolar lavage fluid, as well as tissue histamine content were quantified. Mast cells and eosinophils were detected by histology. Both the early and late phase of airway responses were induced by inhalation of compound 48/80. Histamine and TNF-alpha levels increased significantly 30 min after challenge, but no increases were detected at either 8 or 24 h after challenge. A high LTC(4) level was detected in 30 min and 8 h after challenge. Tissue histamine content decreased at 30 min after challenge and returned to the unstimulated level by 8 h. Connective tissue mast cells in rat trachea showed a degranulation response. Along with the increase in numbers of mucosal mast cells, rat mast cell protease II at both mRNA and protein levels in the trachea epithelial layer was also increased significantly at 30 min after challenge. We conclude that compound 48/80 inhalation causes both the early and late phase of airway contraction in rats. Mast cell degranulation is responsible for the early phase of airway response, which subsequently triggers the late phase of airway response.
Liu
Shuang
S
Department of pharmacology, Ehime University School of Medicine, Shitsukawa, Toon-shi, Japan.
Hiedayati
Nurul
N
Shudou
Masachika
M
Maeyama
Kazutaka
K
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015550:Cell Degranulation / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D007274:Injections, Intraperitoneal; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D017997:Leukotriene C4; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus