Lung surfactant suppresses oxygen-dependent bactericidal functions of human blood monocytes by inhibiting the assembly of the NADPH oxidase.
Surfactant is known to lower the surface tension in alveoli and affects the antibacterial functions of alveolar and peritoneal macrophages. We investigated the effects of surfactant on the bactericidal functions and oxidative metabolism of human blood monocytes and granulocytes. Monocytes incubated with surfactant ingest this material and subsequently exhibit an impaired ability to kill ingested bacteria. Granulocytes incubated with surfactant do not ingest this material, and their bactericidal functions are not affected. However, granulocytes that have ingested surfactant-coated Staphylococcus aureus display an impaired ability to kill these bacteria. Moreover, in monocytes and granulocytes that contain surfactant--the latter by ingestion of surfactant-coated S. aureus--the intracellular production of H2O2 is impaired due to inhibition of the assembly of the NADPH oxidase. Together these results demonstrate that surfactant inside monocytes and granulocytes inhibits the capacity of these cells to kill bacteria intracellularly by impairing oxygen-dependent killing mechanisms.
Geertsma
M F
MF
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Broos
H R
HR
van den Barselaar
M T
MT
Nibbering
P H
PH
van Furth
R
R
D001770:Blood Bactericidal Activity / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D009000:Monocytes / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D019255:NADPH Oxidases; D010100:Oxygen / Q000097:blood*; D010587:Phagocytosis / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development
D011663:Pulmonary Surfactants; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D016650:Fluorescein-5-isothiocyanate; D010100:Oxygen