Bacteria associated with obstructive pulmonary disease elaborate extracellular products that stimulate mucin secretion by explants of guinea pig airways

Abstract

Certain cell-free filtrates from broth cultures of Pseudomonas aeruginosa, Hemophilus influenzae and Streptococcus pneumoniae stimulate secretion of glycoconjugates by explants of guinea pig trachea. The stimulatory effect is not related to toxicity or damage to the respiratory mucosa, as well as could be determined by ultrastructural examination of the explants after exposure. Bacteria isolated from patients with a history of chronic obstructive lung disease (P aeruginosa from cystic fibrosis, H influenzae, and S pneumoniae from chronic bronchitis) do not demonstrate increased frequency of positive strains or greater stimulation of secretion than organisms isolated from other individuals. At least three stimulatory substances are found in cell-free filtrates of P aeruginosa. They appear to be proteins of molecular weight 60,000-100,000 as determined by gel filtration. Within the crude filtrate, they are relatively stable to heat, proteolysis, and storage at 4 C and in liquid nitrogen. The stimulatory activity is not lost upon subculture of the bacteria. When isolated from the filtrate by column chromatography, they become labile to heat and trypsin. Isolated active fractions show proteolytic activity coinciding with mucin-stimulating capacity, suggesting a relationship with Pseudomonas proteases. Stimulatory substances released by S pneumoniae and H influenzae appear to be different from those elaborated by Pseudomonas. They are extremely labile to heat and storage, and the capacity to stimulate secretion is lost on subculture. Preliminary gel filtration indicates the S pneumoniae stimulatory substance(s) is in a molecular weight range of 100,000-300,000 daltons, while that of H influenzae is between 50,000 and 200,000. The results suggest bacteria which chronically infect or colonize respiratory airways of individuals suffering from obstructive lung disease can elaborate extracellular product(s) capable of stimulating secretion of mucin. Thus, the bacteria themselves may contribute to local manifestations and, ultimately, to the pathogenesis of obstructive disease.