Rôle of surfactant free fatty acids in antimicrobial defenses

Previous studies of the mechanisms of killing of inhaled bacteria have been confined to the demonstration that alveolar macrophages phagocytose and kill inhaled staphylococcus intracellularly. We have found recently th at the surfactant-containing fraction of rat bronchoalveolar lavage fluid is bactericidal for pneumococci and some other gram-positive bacteria, excluding staphylococci. In studies reviewed herein, we show that these antibacterial factors in rat surfactant are long-chain free fatty acids (FFA). Polyunsaturated FFA appear to be particularly active. Because inhaled pneumococci are cleared very rapidly in vivo in the absence of conventional opsonins, we speculate that FFA may have a rôle in pneumococcal killing. All species tested to date, including humans, dogs, and guinea pigs have detectable FFA in their surfactant, although the level of FFA in these species is lower than in rats. Human and guinea pig surfactant, in fact, have too little FFA in their pulmonary surfactant to give detectable antipneumococcal activity in vitro. Nonetheless, inhaled pneumococci are killed rapidly by guinea pigs, suggesting that the level of FFA in bronchoalveolar lavage is not a good indication of the amount of FFA on alveolar surfaces, or, alternatively that FFA may not play a rôle in pneumococcal clearance in vivo. We have recently completed histological studies which demonstrate that inhaled pneumococci are, in fact, killed extracellularly in rats. This observation adds credence to the concept that mechanisms exist in the alveoli for extracellular killing of some bacteria and indicates that further studies of FFA in this process are worthwhile.