A possible role of airway epithelium in modulating hyperresponsiveness

Abstract

1In order to examine the role of airway epithelium in the responsiveness of smooth muscle in man, we measured the contractile responses to acetylcholine (ACh), histamine, and prostaglandin F2, (PGF2,) and the relaxation response to isoprenaline (Isop), in 48 bronchi obtained from 10 patients who received surgery. Responses were measured in the presence and absence of the epithelium. 2 Removal of epithelium (by rubbing the mucosa gently with forceps) significantly increased the contractile responses evoked by ACh, histamine and PGF2,.3 In contrast, removal of epithelium did not alter the relaxation response to Isop. 4 To clarify the mechanism underlying this epithelial inhibitory effect on smooth muscle contraction, we measured the contractile responses of dog trachea with the epithelium removed to increasing concentrations of ACh. After measuring the control response, we added about 0.1 g of the chopped epithelium in the organ chamber, and measured the response again. 5 After adding airway epithelium and incubating with tracheal strips, the contractile response of tracheal strips decreased significantly as compared to the control response. 6 These results show that airway epithelium possesses the ability to decrease the smooth muscle contraction to ACh, histamine and PGF2X in man and dogs.7 The mechanism of this inhibitory effect of the airway epithelium is not explained by a change in mechanical property of the airway nor the change in diffusion of these drugs to the smooth muscle across the epithelium. Thus, these results suggest that airway epithelium may have an important role in modulating smooth muscle tone, possibly by inactivation of these mediators, or by releasing an epithelium-derived relaxing factor.

Pharmacological evaluation of a guinea‐pig tracheal epithelium‐derived inhibitory factor (EpDIF)

“…It is now well established in vitro that the epithelium has a significant role to play in modulating airway smooth muscle responsiveness to spasmogenic and relaxant agonists in several species including man (Barnes et al, 1985;Flavahan et al, 1985;Goldie et al, 1986;Raeburn et al, 1986;Aizawa et al, 1988;Vanhoutte, 1988). It has been suggested that the airway epithelium may secrete an inhibitory factor which can modulate airway smooth muscle responsiveness to various agonists (Flavahan et al, 1985).…”

Correlation between airway epithelium‐induced relaxation of rat aorta in the co‐axial bioassay and cyclic nucleotide levels

“…A variety of studies have shown that the sensitivity of airway smooth muscle preparations from various animal species (Barnes et al, 1985;Flavahan et al, 1985;Goldie et al, 1986;Hay et al, 1986) including man Aizawa et al, 1988;Knight et al, 1990) to several bronchoconstrictor agents is significantly increased by removal of the epithelium. These studies have led to the hypothesis that the epithelium can release an inhibitory factor(s) other than prostaglandins (designated as epithelium-derived inhibitory or relaxing factor, EpDIF/ EpDRF; Farmer, 1988;Fedan et al, 1988;Vanhoutte, 1988;Goldie et al, 1990;Raeburn, 1990).…”

Evidence for preservation of epithelial function in cryopreserved porcine and human bronchi

“…Evidence for this comes from the observation that mechanical removal of epithelium increases the sensitivity to a variety of spasmogens of isolated airway smooth muscle from both animals (Goldie, Fernandes, Farmer & Hay, 1990) and humans (Raeburn, Hay, Farmer & Fedan, 1986;Aizawa, Miyazaki, Shigematsu & Tomooka, 1988;Fernandes et al 1989Fernandes et al , 1990. More direct evidence for the release of an epithelium-derived inhibitory factor (EpDIF) has been provided by the coaxial bioassay, consisting of an assay preparation mounted within the lumen of an airway tube segment, which was first described by Ilhan & Sahin (1986).…”

“…Except for a few reports on human airway epithelium (Raeburn et al 1986;Aizawa et al 1988;Fernandes et al 1989Fernandes et al , 1990 …”