Alveolar macrophage function is selectively altered after endotoxemia in rats.
The alveolar macrophage (AM) is exquisitely sensitive to activation by gram-negative bacterial endotoxin, an agent associated with adult respiratory distress syndrome. We tested the hypothesis that specific functions of the AM are activated selectively by in vivo endotoxin while others remain unaffected. AMs were recovered from the airspaces of control and endotoxin-treated (5.0 mg/kg) rats, and functional assays were performed. We measured macrophage adherence, viability, and survival; chemotactic movement; hydrogen peroxide production; phagocytic function; and the secretion of representative biological response modifiers. Endotoxemia enhanced AM adherence during a 15-h incubation period, while not affecting cell number or viability. There was a 60% reduction in AM chemotactic movement and a 65% augmentation of hydrogen peroxide production, but no effect on AM phagocytosis of Staphylococcus aureus. Endotoxemia enhanced AM production of macrophage-derived chemotactic activity for neutrophils by 70% and interleukin-1 activity by 100%, but did not affect the production of macrophage-derived growth factor activity for fibroblasts. We conclude that endotoxemia alters the functions of the AM in a selective manner; certain functions are enhanced, while others are inhibited or not affected. We believe that this selective effect on AM functional capacity may be an important mechanism explaining certain aspects of the course, duration, or outcome of adult respiratory distress syndrome associated with gram-negative sepsis.
Christman
J W
JW
Department of Internal Medicine, University of Vermont, Burlington 05405.
Petras
S F
SF
Hacker
M
M
Absher
P M
PM
Davis
G S
GS
D000818:Animals; D002448:Cell Adhesion; D002470:Cell Survival; D002630:Chemotactic Factors / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte; D004731:Endotoxins / Q000097:blood*; D006133:Growth Substances / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology*; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000166:cytology / Q000503:physiopathology*; D051381:Rats
D002630:Chemotactic Factors; D004731:Endotoxins; D006133:Growth Substances; D007375:Interleukin-1; D006861:Hydrogen Peroxide