Modulation of rabbit airway smooth muscle responsiveness by respiratory epithelium. Involvement of an inhibitory metabolite of arachidonic acid.

The integrity of the respiratory epithelium may be important in development of bronchial hyperreactivity; however, the mechanisms involved remain unknown. This study was undertaken to determine if epithelium of rabbit intrapulmonary bronchi is capable of modulating the responsiveness of airway smooth muscle to a pharmacologic stimulus, and whether epithelial-derived prostaglandins play a role in this modulatory function. Mechanical removal of the epithelium from bronchial segments, or incubation of intact bronchi with indomethacin (an inhibitor of prostaglandin synthesis) increased the sensitivity of bronchial smooth muscle to bethanechol. Cyclooxygenase was localized within mucosal epithelial cells of intact airways by avidin-biotin immunoperoxidase staining using a monoclonal antibody to the enzyme. Removal of the epithelium significantly reduced the levels of PGE2 and 6-keto-PGF1 alpha accumulated in the media surrounding bronchial explants. In epithelium-intact bronchi precontracted with bethanechol, arachidonic acid evoked an indomethacin-sensitive relaxation response comparable to relaxation induced by exogenous addition of PGE2. Although PGE2 evoked similar responses in epithelium-denuded bronchi, arachidonic acid-induced relaxation responses were negligible. The results suggest epithelial cells of rabbit bronchi modulate the responsiveness to pharmacologic stimuli by production and release of an inhibitory cyclooxygenase metabolite of arachidonic acid.

Physical and biological properties of cyclopolymers related to DIVEMA ("pyran copolymer").

A series of copolymers related in structure to the 1:2 alternating cyclocopolymer of divinyl ether and maleic anhydride (DIVEMA) have been shown to possess antitumor properties. The synthesis and structures of these copolymers are discussed, and their effectiveness as antitumor agents is presented. Certain of the copolymers have been prepared in controlled molecular weight ranges using chain transfer agents, and the resultant copolymers finally fractionated via use of solvent-nonsolvent systems. These samples of narrow molecular weight distribution have been evaluated for their antitumor properties and have been found to be quite effective.

Interaction of Mount St. Helens' volcanic ash with cells of the respiratory epithelium.

Respirable-sized dust from the Mount St. Helens (MSH) eruption of Spring 1980, and minerals similar to the major components of the volcanic ash, were examined comparatively for interactions with epithelial cells of rodent respiratory airways in vitro. MSH dust, Na feldspar, cristobalite, and alpha-quartz, in concentrations of 0.4 to 40 mg/ml, had neither significant effects on mucin release by tracheal explants nor acute toxic effects after exposure for 2 hr. Long-term incubation (1 and 3 weeks) of explants after a 1-hr exposure to MSH dust failed to elicit widespread toxic or proliferative changes in airway epithelial cells. In contrast, long-term exposure to Na feldspar, cristobalite, and alpha-quartz caused significant toxicity to the explants, although metaplastic changes were not observed. Ultrastructural evidence of associations (e.g., phagocytosis) between particulates and respiratory epithelium was not observed. The results of these studies suggest that volcanic ash from MSH interacts minimally with cells of the respiratory mucosa.