A comparative study on the release of leukotrienes and histamine by guinea pig lung and trachea after challenge with antigen or stimulation with ionophore A23187 or melittin

Abstract

The release of leukotrienes and histamine from guinea pig lung and trachea after immunological and nonimmunological stimulation were compared. Antigen, ionophore A23187 and melittin caused the release of leukotriene (LT)B4, LTC4, LTD4 and LTE4 from lung and trachea as determined by reverse-phase high performance liquid chromatography (RP-HPLC) and bioassay. The release of LTB4 by lung and trachea was maximum after 5 min of ionophore stimulation (128 +/- 40 and 142 +/- 29 pmol/g tissue, respectively). Lung, but not trachea, also released the 20-OH-LTB4 and 20-COOH-LTB4. The release of LTC4 by lung tissues was maximum after 5 min, whereas maximal tracheal responses occurred at 10 min (27 +/- 11 and 9 +/- 3.5 pmol/g tissue, respectively). Maximal release of LTD4 by lung and trachea respectively occurred after 10 and 15 min (103 +/- 21 and 20 +/- 6 pmol/g tissue, respectively). The release of LTD4 in response to ionophore by both tissues decreased after 15 min, whereas the release of LTE4 continued to increase. Release of leukotrienes from melittin stimulated lung was 2-3-fold less than in ionophore stimulation. In contrast, tracheal responses to melittin and ionophore for the release of LTB4 were equivalent, whereas release of peptidoleukotrienes in response to melittin was approximately 50% that resulting from ionophore. Antigen challenge was the least potent stimulus for LTB4 release in both tissues, whereas it was at least as potent as melittin for the release of peptidoleukotrienes. The release of histamine by lung tissue was approximately 2-3-fold greater than by trachea (7 +/- 1 and 2 +/- 0.5 nmol/g tissue, respectively) after 5 min of stimulation with either ionophore, melittin or antigen. These data demonstrate that lung tissues and trachea respond to immunologic stimulations by releasing the mediators of inflammation and immediate hypersensitivity. The lung releases peptidoleukotrienes and histamine 2-5-fold greater than the trachea, whereas the release of LTB4 in both tissues are approximately equal.