Release of epithelium-derived PGE₂from canine trachea after antigen inhalation

Abstract

To investigate the role of prostaglandin (PG) E2 in allergen-induced hyperresponsiveness, dogs inhaled either the allergen Ascaris suum or vehicle (Sham). Twenty-four hours after inhalation, some animals exposed to allergen demonstrated an increased responsiveness to acetylcholine challenge in vivo (Hyp-Resp), whereas others did not (Non-Resp). Strips of tracheal smooth muscle, either epithelium intact or epithelium denuded, were suspended on stimulating electrodes, and a concentration-response curve to carbachol (10−9 to 10−5 M) was generated. Tissues received electrical field stimulation, and organ bath fluid was collected to determine PGE2content. With the epithelium present, all three groups contracted similarly to 10−5 M carbachol, whereas epithelium-denuded tissues from animals that inhaled allergen contracted more than tissues from Sham dogs. In response to electrical field stimulation, Hyp-Resp tissues contracted less than Sham tissues in the presence of epithelium and more than Sham tissues in the absence of epithelium. PGE2release in the muscle bath was greater in Non-Resp tissues than in Sham or Hyp-Resp tissues when the epithelium was present. Removal of the epithelium greatly inhibited PGE2release. We conclude that tracheal smooth muscle is hyperresponsive in vitro after in vivo allergen exposure only when the modulatory effect of the epithelium, largely through PGE2 release, is removed.

Bacterial Challenge Stimulates Formation of Arachidonic Acid Metabolites by Human Keratinocytes and Neutrophils In Vitro

“…These findings indicate that epithelial cells are an integral part of the immune system, eliciting proinflammatory responses to a bacterial challenge. In contrast to experiments that demonstrated the synthesis of anti-inflammatory mediators by airway epithelial cells upon antigen stimulation in animal experiments and in vitro (25,30,35), the present investigation clearly indicates that the reaction of keratinocytes to a bacterial challenge was dominated by the synthesis of proinflammatory arachidonic acid mediators. The released arachidonic acid mediator PGE 2 is able to affect other inflammatory cells, like the modulation of T-lymphocyte lymphokine secretion and cytotoxicity (18) or the stimulation of immunoglobulin production by B cells (20,32).…”

Effects of furosemide on allergic asthmatic responses in mice

“…It is well known that contraction of airway smooth muscle can be affected by events taking part in the airway that are independent of the airway smooth muscle itself. For example, mediators released from the airway epithelium, including prostaglandin E2 can regulate the magnitude of induced contraction [27]. We have no direct evidence implicating a specific mechanism for the observed effect of NKCC1 inhibition, but our findings support further investigations into such mechanisms.…”

Chlorine-induced Injury to the Airways in Mice

“…After 100 ppm chlorine there was a reduction in respiratory system resistance, suggesting the possibility of a bronchodilatory mechanism that was triggered by exposure to lower levels of chlorine. The airway epithelium itself is a likely source of bronchodilatory substances such as prostanoids (22) and nitric oxide (23). Indeed, there was an increase in nitric oxide production as reflected in nitrite/nitrate levels in the lung lavage fluid after the 100 ppm exposure.…”