Response of alveolar macrophage-depleted rats to hyperoxia.
Recently an alveolar macrophage (AM)-depleted rat model has been characterized and it has been demonstrated that AM are required for the endotoxin-induced tumor necrosis factor (TNF) release into the alveolar space (J Appl Physiol 1993;74:2812-2819). The current study investigated the response of AM-depleted rats to hyperoxia and evaluated the potential role of AM in the pathogenesis of pulmonary O2 toxicity. Rats were insufflated with Hanks' balanced salt solution (HBSS), liposome-encapsulated phosphate-buffered saline (PBS-liposomes), or liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP-liposomes) and 2 days later exposed to 100% O2. The effect of hyperoxia was assessed by parameters of O2-induced lung injury (e.g., hematocrit value, pleural effusion volume, effusion protein to plasma protein ratio, and alveolar lavage fluid protein content), TNF release into the alveolar space, and survival. Insufflation of Cl2MDP-liposomes, but not HBSS or PBS-liposomes, caused a sustained depletion of > 70% AM, which was associated with a slight but significant increase in the number of lavageable neutrophils. Twenty percent of AM-depleted rats survived longer than 74 h of O2 exposure, while all rats insufflated with HBSS or PBS-liposomes died within 74 h (p < .05). No significant differences were detected in alveolar TNF release or in the extent of O2-induced lung injury.
Berg
J T
JT
Research Service, Samuel S. Stratton Department of Veterans Affairs Medical Center, Albany, NY 12208.
White
J E
JE
Tsan
M F
MF
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004002:Clodronic Acid / Q000008:administration & dosage; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000473:pathology / Q000503:physiopathology*; D007327:Insufflation; D008081:Liposomes; D008168:Lung / Q000187:drug effects; D055370:Lung Injury; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008081:Liposomes; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid