On the mechanism of histamine release from pig lung in vitro induced by extracts of cotton dust.

Abstract

A water-soluble agent which releases histamine from human and pig lung in vitro is present in dust from the cardrooms of cotton mills [1, 2]. There is also evidence that the acute changes in respiratory function observed in volunteers after inhalation of cotton dust are associated with a release of histamine [3]. In the present study the nature of the histamine releasing mechanism has been examined using an in vitro technique in which aqueous extracts of cotton dust were incubated with chopped pig lung [2]. The amount of water-soluble extractives is expressed in terms of the weight of cotton dust from which it had been derived. At pH 7.4 a dose-response relationship for histamine release was exhibited over the concentration range 10-150 mg cotton dust/ml of incubation medium, and up to 15% of the total lung histamine was released at the maximally effective level. The histamine releasing activity of cotton dust (27 mg/ml) was both temperatureand pH-dependent, the optima being 37 ~ and pH 7.4 respectively. However, at a concentration of 83 mg/ml, histamine release was increased when the pH was raised from 7.4 to 8.2. A Ca/Mg-free medium inhibited the release of histamine by 27 mg/ml of Cotton dust. In the absence of glucose, potassium cyanide (10 -3 M) reduced the histamine released by 27 mg/ml of cotton dust by 25%, but potentiated the activity of 83 mg/ml of the dust. The inclusion in the medium o f either 2,4-dinitrophenol (5 x 10-4 M glucose-free medium), ninhydrin (10 .3 M ) o r N-ethylmaleimide reduced the histamine releasing activity of 27 mg/ml of cotton dust by 95%, 55% and 30% respectively. These results are interpreted as indicating that in pig lung the cotton dust-mediated histamine release appears to be largely an energy-dependent mechanism. However, at a dust concentration of 83 mg/ml an energyindependent mechanism may also operate.