Effects of Leukotriene B₄Inhalation: Airway Sensitization and Lung Granulocyte Infiltration in the Guinea Pig

Abstract

Male Hartley guinea pigs were exposed by inhalation to leukotriene B4 (LTB4) and challenged 5 min or 4 h later with bronchoconstrictive aerosols of histamine or the divalent cationic ionophore A23187. Pulmonary gas trapping measured in excised lungs indicated the severity of post-challenge airway obstruction. Airway granulocyte infiltration was scored by an observer who was unaware of animal assignments. Treatment with LTB4 produced a marked influx of eosinophils and neutrophils into tracheal and bronchial airways. Granulocyte scores for LTB4-treated groups were 1.9 to 3.3 times higher than those for vehicle-treated groups at 5 min after exposure and 3.3 to 10.7 times higher at 4 h after exposure. Leukotriene B4 itself did not produce hyperinflation. However, histamine-induced gas trapping was increased 5 min after LTB4 exposure. Histamine responsiveness was unaffected 4 h after LTB4 treatment. In contrast, A23187-induced gas trapping was unaffected at 5 min, but diminished at 4 h after LTB4. Nonchemotactic stereoisomers of LTB4 did not produce granulocyte influx, but did produce altered airway responses similar to those seen for LTB4. We conclude that inhaled LTB4 produces airway granulocyte infiltration in the guinea pig and alterations in airway responsiveness that vary with the challenge stimulus and time after exposure. Alterations in airway responses may result from granulocyte-independent effects of LTB4 and its stereoisomers.

Bradykinin Induces Eosinophil Accumulation in the Rat Pleural Cavity

“…This hypothesis is also supported by findings concern ing another more selective lipoxygenase inhibitor, BW A4C [9], which as shown here also abolished the pleural eosinophil accumulation induced by bradyki nin. It is noteworthy that inhalation of the lipoxyge nase metabolite LTB4 induces lung eosinophil infil tration in guinea pig [17] and also attracts eosinophils, when intrathoracically injected into rats (data not shown), adding support to the interpretation that the pleural eosinophilia by bradykinin might account for the secondary release of LTB4. Interestingly, the in jection of bradykinin into the rat pleural cavity also resulted in an accumulation of neutrophils which peaked 6 h after the agonist.…”

A23187-induced pulmonary gas trapping and inflammation in the guinea pig

“…Since lung tissue density approximates that of saline, the volume of gas trapped in the lungs could then be determined from the difference in weight of the brass anchor and the brass anchor plus lungs. Histological evaluation procedures were similar to those previously described [19]. Following ELGV determinations, the lungs were infused via the trachea with 7 ml of 10% phosphate-buffered formalin.…”

Effects of leukotriene B 4 receptor antagonist, LY293111Na, on antigen-induced bronchial hyperresponsiveness and leukocyte infiltration in sensitized guinea pigs

“…LTB 4 has been found in the bronchoalveolar lavage (BAL) fluids of asthmatic patients [5]. This C-20 fatty acid is a potent chemoattractant of both neutrophils and eosinophils and may also produce BHR to spasmogens such as histamine or acetylcholine [6,7]. The reduction of LTB 4 activity by its antagonists might lead to the control of airway inflammation and BHR.…”