Airway mucin secretion and MC (mast cell) degranulation must
be tightly controlled for homoeostasis of the lungs and immune
system respectively. We found the exocytic protein Munc18b
to be highly expressed in mouse airway epithelial cells and
MCs, and localized to the apical pole of airway secretory cells.
To address its functions, we created a mouse with a severely
hypomorphic Munc18b allele such that protein expression in
heterozygotes was reduced by∼50%. Homozygous mutant mice
were not viable, but heterozygotes showed a ∼50% reduction
in stimulated release of mucin from epithelial cells and granule
contents from MCs. The defect in MCs affected only regulated
secretion and not constitutive or transporter-mediated secretion.
The severity of passive cutaneous anaphylaxiswas also reduced by
∼50%, showing that reduction of Munc18b expression results
in an attenuation of physiological responses dependent on MC
degranulation. The Munc18b promoter is controlled by INR
(initiator), Sp1 (specificity protein 1), Ets, CRE (cAMP-response
element), GRE (glucocorticoid-response element), GATA and
E-box elements in airway epithelial cells; however, protein levels
did not change during mucous metaplasia induced by allergic
inflammation. Taken together, the results of the present study
identifyMunc18b as an essential gene that is a limiting component
of the exocytic machinery of epithelial cells and MCs