Influence of indomethacin and l-cysteine on histamine and peptidoleukotriene release from superfused tracheas taken from guinea pigs passively sensitized with IgG1 and IgE antibodies

Abstract

We have previously reported differences in mediator release during equivalent levels of antigen (Ag)-induced smooth muscle contraction of guinea pig pulmonary tissues after passive sensitization with IgG1 versus IgE antibodies (Abs). In the present study, we have examined the influence of indomethacin (5 x 10 −6 mol/L) and l-cysteine (3 or 10 mmol/L) on mediator release from superfused trachea taken from guinea pigs passively sensitized with IgG1 or IgE Ab 1 day before in vitro studies. Tissues were challenged with Ag (oxazolone-human serum albumin conjugate), and contractions and superfusate histamine and peptidoleukotrienes were monitored at discrete time intervals thereafter. Superfusate mediator contents were determined by spectrophotofluorimetry (histamine) and RAST (peptidoleukotrienes). The profiles of peptidoleukotrienes were examined with high-pressure liquid chromatography. At equivalent levels of contraction, significantly less histamine and peptidoleukotrienes were found in superfusate samples after sensitization with IgE Abs. None of the drug pretreatments significantly altered Ag-induced histamine release after IgGI or IgE sensitization. Indomethacin resulted in an increase in total measurable peptidoleukotrienes found only after IgGI receptor activation, but it did prolong tracheal contractions with both Abs. l-cysteine, 10 mmol/L, resulted in an increase in total measurable superfusate peptidoleukotriene content under all experimental conditions. The percentage increase in peptidoleukotriene content from that found without drug pretreatment was larger in the case of IgE compared to IgGI sensitization. During early time periods, after Ag challenge, measurable peptidoleukotriene levels in superfusate samples were similar for both Abs in the presence of l-cysteine, 10 mmol/L. These data suggest that there is a differential pattern of peptidoleukotriene metabolism after activation of IgG1 versus IgE receptors in guinea pig trachea.