Epithelium-derived inhibitory factor in human bronchus.
The potencies of histamine and methacholine were significantly increased by approximately 2- and 5-fold respectively in human non-diseased isolated bronchi on removal of the epithelium. In contrast, no increases in spasmogen potency were observed following epithelium removal in bronchi obtained from a sample of asthmatic human lung. The failure of epithelium removal to increase asthmatic bronchial sensitivity to histamine may have been due to a reduction in the release of an epithelium-derived inhibitory factor (EpDIF) resulting from disease-induced epithelial damage. A co-axial bioassay system in which endothelium-denuded rat aorta was used as the assay tissue was used to detect the release of a vasorelaxant EpDIF from human bronchial tissue. Histamine (100 microM) and methacholine (25 microM), in the presence of indomethacin (5 microM), reduced phenylephrine-induced tone in endothelium-denuded rat aorta in co-axial assemblies by 75 +/- 11 and 67 +/- 9% respectively. Removal of the bronchial epithelium abolished these responses, indicating that they were mediated by an EpDIF. It is possible that human airway smooth muscle is sensitive to this vasorelaxant EpDIF and that the absence of the source of this factor following epithelium removal caused the increases in sensitivity to spasmogens. Alternatively, the human bronchial epithelium may also release an EpDIF selective for airway smooth muscle.
Fernandes
L B
LB
Department of Pharmacology, University of Western Australia, Perth.
Preuss
J M
JM
Paterson
J W
JW
Goldie
R G
RG
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001685:Biological Factors / Q000502:physiology*; D001980:Bronchi / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001685:Biological Factors; D008688:Methacholine Compounds; C067763:epithelium-derived inhibitory factor; D010656:Phenylephrine; D006632:Histamine; D002217:Carbachol; D007213:Indomethacin