Extracellular killing of inhaled pneumococci in rats.
Early clearance of inhaled Staphylococcus aureus is believed to be caused by phagocytosis by alveolar macrophages. In murine models inhaled pneumococci are cleared even more rapidly than S. aureus. Conventional opsonins appear to play no role in this clearance, and recently it has been shown that murine alveolar lining material contains free fatty acids and other soluble factors that are directly bactericidal for pneumococci. To determine whether non-phagocytic factors are involved in pneumococcal clearance, we compared the site of killing of inhaled pneumococci and S. aureus in rats using histologic methods and bronchoalveolar lavage. Spontaneous lysis of pneumococci was prevented by use of autolysin-defective pneumococci or by substitution of ethanolamine for choline in the cell wall. Histologic studies showed that the percent of inhaled staphylococci associated with alveolar macrophages always exceeded the percent of staphylococci cleared, whereas there was little association of pneumococci with macrophages during clearance. Analysis of the intracellular or extracellular location of iron 59 in bronchoalveolar lavage fluid of rats that had inhaled aerosols of 59Fe-labeled bacteria suggested that staphylococci were killed predominantly in macrophages and pneumococci in the extracellular space. When 59Fe-labeled pneumococci or staphylococci were ingested and killed by macrophages in vitro, the 59Fe remained with the macrophages, suggesting that the extracellular location of 59Fe during pneumococcal killing in vivo was not caused by rapid turnover of 59Fe in macrophages. Studies of the site of killing of inhaled type 25 pneumococci labeled exclusively in the cell wall with carbon 14-ethanolamine confirmed the results obtained with 59Fe-labeled pneumococci. Thus, early killing of inhaled pneumococci, unlike staphylococci, appears to take place outside of macrophages.
Coonrod
J D
JD
Department of Medicine, Veterans Administration, Medical Center, Lexington, KY.
Marple
S
S
Holmes
G P
GP
Rehm
S R
SR
D000280:Administration, Inhalation; D000818:Animals; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D007504:Iron Radioisotopes; D008264:Macrophages / Q000276:immunology; D008297:Male; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000166:cytology; D011663:Pulmonary Surfactants / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013211:Staphylococcus aureus; D013296:Streptococcus pneumoniae; D007507:Therapeutic Irrigation
D004983:Ethanolamines; D005230:Fatty Acids, Nonesterified; D007504:Iron Radioisotopes; D011663:Pulmonary Surfactants; D019856:Ethanolamine