A mechanism of antigen-induced goblet cell degranulation in the nasal epithelium of sensitized rats.
BACKGROUND
We have produced hypertrophic and metaplastic changes of goblet cells in nasal epithelium of ovalbumin (OVA)-sensitized rats by intranasal challenge with OVA. A variety of allergic mediators and inflammatory cells are capable of stimulating goblet cell degranulation (epithelial mucus secretion); however, little is known about the mechanism by which antigen induces mucus hypersecretion.


OBJECTIVE
Our aim was to explain the mechanism of goblet cell degranulation in allergic inflammation.


METHODS
Antigen-induced goblet cell degranulation was evaluated by the transient decrease of epithelial mucosubstance 1 to 6 hours after intranasal challenge with OVA in nasal epithelium of OVA-sensitized rats. The effects of the H(1)-antagonist (d -chlorpheniramine malate), H(2)-antagonist (cimetidine), atropine, indomethacin, cysteinyl leukotriene (cysLT) antagonist (ONO1078), and antirat PMN antiserum on OVA-induced goblet cell degranulation were examined.


RESULTS
Goblet cell secretion 1 hour after OVA challenge was significantly inhibited by H(1)-antagonist, atropine, and cysLT antagonist, whereas the secretion 6 hours after the challenge was significantly inhibited by cysLT antagonist and antirat PMN antiserum. Circulating PMN cells and mucosal infiltrating eosinophils were completely abolished by antirat PMN antiserum.


CONCLUSIONS
These results indicate the different mechanisms of goblet cell secretion between early-phase (1 hour after OVA challenge) and late-phase (6 hours after the challenge) reactions. Histamine stimulates early-phase secretion through the H(1)-receptor of cholinergic nerve terminals, and infiltrating inflammatory cells (eosinophils and/or neutrophils) play a role in late-phase secretion. CysLTs (leukotrienes C(4), D(4), and E(4)) are important for both early-phase and late-phase secretion.
Shimizu
Takeshi
T
Department of Otorhinolaryngology, Mie University School of Medicine, Japan.
Shimizu
Shino
S
Hattori
Reiko
R
Majima
Yuichi
Y
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001285:Atropine / Q000494:pharmacology; D015550:Cell Degranulation; D002867:Chromones / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004804:Eosinophils / Q000502:physiology; D006632:Histamine / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D009093:Mucus / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats
D000941:Antigens; D002867:Chromones; D001285:Atropine; D002927:Cimetidine; D006632:Histamine; D010047:Ovalbumin; C047681:pranlukast; D007213:Indomethacin