Artificial surfactant (Surfactant TA) modulates adherence and superoxide production of neutrophils.
Neutrophils cause lung injuries by releasing proteases and active oxygen radicals in patients with acute respiratory distress syndrome (ARDS). Artificial surfactant is used to replace native surfactant whose functions are deteriorated by serum-derived inhibitors in these patients. We investigated potential interactions between exogenous surfactant (Surfactant TA) and neutrophils in in vivo and in vitro experimental models. Neutrophil alveolitis was induced in hamster lungs by the intratracheal administration of bleomycin (5 mg/kg) on Day 0. Some of the animals were followed by replacement with Surfactant TA (5 and 10 mg/100 g body weight) on Day 1. Alveolar cells were harvested by lung lavage on Day 2. The numbers of the neutrophils obtained from the lungs treated with bleomycin and Surfactant TA were unchanged, but the superoxide production from these cells was significantly decreased when compared with control animals (no Surfactant TA). From the in vitro experiments, Surfactant TA was shown to inhibit adherence and superoxide production of human neutrophils. These effects were derived from the heat-resistant components of Surfactant TA and were mimicked by treatment with liposomes of dipalmitoyl phosphatidylcholine. Surfactant-TA-treated neutrophils were demonstrated to have picnotic nuclei and to express Fas antigens, which were characteristic of apoptotic cells. These results suggest that exogenous Surfactant TA may play an important role not only in improving surfactant functions but in preventing neutrophils from further activation, probably through enhancing apoptosis.
Suwabe
A
A
Department of Laboratory Medicine, First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
Otake
K
K
Yakuwa
N
N
Suzuki
H
H
Ito
M
M
Tomoike
H
H
Saito
Y
Y
Takahashi
K
K
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000009:adverse effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count; D008081:Liposomes; D008168:Lung / Q000473:pathology; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000473:pathology; D013481:Superoxides / Q000378:metabolism*; D019014:fas Receptor / Q000032:analysis
D000900:Anti-Bacterial Agents; D008081:Liposomes; D011663:Pulmonary Surfactants; D017382:Reactive Oxygen Species; D019014:fas Receptor; D001761:Bleomycin; D013481:Superoxides; D015060:1,2-Dipalmitoylphosphatidylcholine; D010450:Endopeptidases