Shift in subfractions of rat alveolar macrophages in vivo during endotoxin-induced alveolitis.
To elucidate changes in alveolar macrophages that accompany sepsis-induced lung injury, this study analyzed the subfractions of alveolar macrophages (AM) recovered by lung lavage during the onset of endotoxin-induced acute neutrophilic alveolar inflammation in the rat model. Centrifugation on continuous self-generated density gradients of Percoll was used to fractionate AM into subpopulations between density limits 1.012 and 1.130. Two-thirds of AM recovered from pathogen-free control rats (group C) were in a fraction with a density range of 1.058-1.078 ["normal" density fraction, (ND)]. Only 6% were located in a very low density (VLD) fraction 1.037-1.048. Neutrophils accounted for less than 1% of recovered cells and usually were found in the fraction with density range of 1.079-1.130. By contrast, if rats underwent lung lavage 15 hours after the administration of endotoxin (group E), only 38% of macrophages were recovered in the "normal" density fraction, whereas 26% of the AM recovered were in the VLD fraction. This shift in the relative sizes of the density based subpopulations coincided with the onset of acute bronchoalveolar inflammation as indicated by the recovery of neutrophils by bronchoalveolar lavage (PMN = 7 X 10(4) in C, vs. 9.4 X 10(5) in E, p less than .001). The macrophages on the low density subfractions showed functional impairment: they were less viable in culture and migrated poorly in response to endotoxin-activated serum compared to macrophages in the "normal" density fraction from the endotoxin-treated animals. The rapid emergence of the low density population after endotoxin could represent an influx of new cells, but more likely indicates that injury to or previous activation of resident macrophages has caused their density to decrease. We speculate that the emergence of a population of AM in airspaces with low density and impaired function could weaken pulmonary host defence following endotoxemia.
D000818:Animals; D002452:Cell Count; D002458:Cell Fractionation; D002465:Cell Movement; D002470:Cell Survival; D004731:Endotoxins / Q000633:toxicity*; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D009504:Neutrophils / Q000473:pathology; D011650:Pulmonary Alveoli / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012128:Respiratory Distress Syndrome / Q000473:pathology
D004731:Endotoxins