Immunosuppressive properties of surfactant in alveolar macrophage NR8383.
OBJECTIVE
To evaluate the anti-inflammatory effects of exogenous surfactants and surfactant phospholipid without surfactant proteins (SP-A and SP-D) on the lipopolysaccharide- (LPS) stimulated rat alveolar macrophage (AM) cell line NR8383.


METHODS
Exogenous surfactants (beractant, calfactant or colfosceril) and surfactant phospholipid (dipalmitoyl phosphatidylcholine, DPPC), standardized to phospholipid content of 25-1,000 microg/ml were incubated with LPS- (1 microg/ml) stimulated NR8383 AMs.


RESULTS
TNF-alpha and IL-1beta secretion and nitric oxide (NO) formation following LPS stimulation were inhibited by treatment with surfactants or DPPC. Furthermore, LPS-dependent NO production and iNOS protein levels were significantly suppressed in cells pretreated for one hour with beractant compared to beractant added simultaneously with or following LPS. Additionally, LPS-stimulated oxidative burst, measured by flow cytometry, was significantly decreased by beractant. Finally, beractant inhibited the translocation of NF-kappaB from cytoplasmic into nuclear extract in LPS-stimulated NR8383 AMs.


CONCLUSIONS
Exogenous surfactants and surfactant phospholipid inhibit secretion of proinflammatory cytokines and NO in NR8383 AMs. The inhibitory effects of beractant on oxygen radical and LPS-induced NO formation may result from unique mechanisms of decreasing cell signaling. The anti-inflammatory activity of surfactant products used in the treatment of neonatal respiratory distress syndrome (RDS) may depend upon the specific preparation or dose used.
Kerecman
J
J
Department of Pediatrics, Wilford Hall USAF Medical Center, San Antonio, USA.
Mustafa
S B
SB
Vasquez
M M
MM
Dixon
P S
PS
Castro
R
R
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000818:Animals; D001688:Biological Products / Q000378:metabolism; D002460:Cell Line; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D011092:Polyethylene Glycols / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000276:immunology*; D051381:Rats; D016897:Respiratory Burst; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D001688:Biological Products; D004338:Drug Combinations; D005233:Fatty Alcohols; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D010767:Phosphorylcholine; D015060:1,2-Dipalmitoylphosphatidylcholine; D009569:Nitric Oxide; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; D052247:Nitric Oxide Synthase Type II; C117342:calfactant; C072197:beractant