NEUROGENIC GOBLET CELL SECRETION AND BRONCHOCONSTRICTION IN GUINEA-PIGS SENSITIZED TO TRIMELLITIC ANHYDRIDE

Trimellitic anhydride is a cause of occupational asthma in humans. We have previously found that tracheal instillation of trimellitic anhydr ide conjugated to guinea pig serum albumin induces acute bronchoconstr iction and airway plasma exudation in sensitised animals, responses me diated primarily via histamine release. In the present study, neural m echanisms mediating bronchoconstriction and goblet cell secretion were determined in trimellitic anhydride-sensitised guinea pigs using the ganglionic blocker hexamethonium to eliminate efferent reflex mechanis ms, pretreatment with capsaicin to eliminate afferent mechanisms, or c imetidine and mepyramine to eliminate histamine-mediated mechanisms. T he magnitude of secretion of intracellular mucus from tracheal goblet cells was quantified morphometrically as a mucus score which is invers ely related to the degree of discharge. Guinea pigs were injected intr adermally either with 0.1 ml 0.3% trimellitic anhydride in corn oil or with corn oil alone as control. Fourteen to eighteen days later all s ensitised animals had developed specific immunoglobulin (Ig) G1 antibo dies whereas the controls had not. Tracheal instillation of conjugated trimellitic anhydride in anaesthetised animals significantly increase d airway lung resistance (R(L)) 24-fold in sensitised guinea pigs (34. 3 +/- 7.9 cm H2O . ml(-1) . s) compared with controls (1.4 +/- 0.1 cm H2O . ml(-1) . s). Mucus score was significantly reduced by 51% (indic ating goblet cell secretion) in sensitised guinea pigs (183 +/- 22 muc us score units) compared with controls (372 +/- 41 mucus score units). The antihistamines significantly inhibited conjugated trimellitic anh ydride-induced bronchoconstriction by 89%, but did not significantly a ffect goblet cell discharge. Hexamethonium alone did not significantly affect conjugated trimellitic anhydride-induced bronchoconstriction o r goblet cell secretion. Capsaicin pretreatment (in combination with h examethonium) significantly inhibited goblet cell discharge (by 80%) b ut had no significant effect on bronchoconstriction. We conclude that conjugated trimellitic anhydride challenge of trimellitic anhydride-se nsitised guinea pigs induces goblet cell discharge and bronchoconstric tion via different mechanisms with activation of capsaicin-sensitive s ensory nerves responsible for secretion and histamine release responsi ble for airway constriction. The guinea pig model of trimellitic anhyd ride-induced occupational asthma may prove useful in examination of me chanisms of goblet cell secretion in allergic diseases.