Am. J. Respir. Crit. Care Med., Volume 158, Number 6, December 1998, 1890-1899

Artificial Surfactant (Surfactant TA) Modulates Adherence and Superoxide Production of Neutrophils

AKIRA SUWABE, KAZUHISA OTAKE, NAOSHI YAKUWA, HIROKI SUZUKI, MIYUKI ITO, HITONOBU TOMOIKE, YASUSHI SAITO, and KEIJI TAKAHASHI

Department of Laboratory Medicine, First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata; Second Department of Internal Medicine, Chiba University, Chiba; and Division of Respiratory Disease, Department of Internal Medicine, Kanazawa Medical University, Kanazawa, Japan

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.

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