Alteration in the modulatory role of respiratory epithelium after exposure of guinea pigs to respirable cotton dust.
Chest tightness may occur after inhalation of cotton dust. To understand the origins of this symptom of byssinosis, we exposed guinea pigs to respirable cotton dust and determined whether the resulting pulmonary obstruction was associated with alterations in the in vitro reactivity of the trachea to methacholine. The isolated, perfused trachea preparation was utilized because it allows a comparison of airway smooth muscle responses to drugs after they are applied separately to the mucosal or serosal surfaces. In epithelium-containing control tracheae, mucosally applied methacholine was less potent and elicited smaller maximum contractile responses than those obtained when it was applied to the serosal compartment. After a 6-h inhalation exposure to 30 mg/m3 respirable cotton dust, the mucosal maximum response to methacholine was substantially increased immediately (0 h) after the end of the exposure, but it was decreased 18 h postexposure. A dust level of 10 mg/m3 produced modest increases in the mucosal maximum responses at both postexposure periods, elevating them to the magnitude of the extraluminal maximum response. The potency of serosally applied methacholine was not affected by any cotton dust exposure. Mechanical epithelium removal increased mucosal reactivity to the serosal level in both control and cotton (30 mg/m3)-exposed groups, and abolished the effects of dust on mucosal reactivity to methacholine. Our findings suggest that the modulatory effect of the epithelium may be inhibitory or excitatory. The balance between the two influences may be altered by inhaled cotton dust.
Smith
J A
JA
Department of Pharmacology and Toxicology, West Virginia University, Morgantown.
Frazer
D G
DG
Fedan
J S
JS
D000280:Administration, Inhalation; D000818:Animals; D002095:Byssinosis / Q000209:etiology; D004391:Dust / Q000009:adverse effects*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D003368:Gossypium / Q000009:adverse effects*; D006168:Guinea Pigs; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D004391:Dust; D016210:Methacholine Chloride