The Effect of Surfactant Protein D in Acute Lung Injury and Pulmonary Fibrosis Induced By Bleomycin

Acute lung injury (ALT), which is associated with a high mortality and morbidity in both infants and adults, is caused by severe lung inflammation resulted from a variety of local and systemic infection such as sepsis and pneumonia. According to the disease procession, there are three stages: exudate formation, proliferation, and fibrosis. Idiopathic pulmonary fibrosis (IPF) is another chronic, progressive and lethal fibrotic lung disease. The etiology of IPF is still unknown. However, both diseases have some similar hallmarks such as hypoxemia and respiratory failure. Surfactant protein D (SP-D), a C-type lectin, which is produced by alveolar type II cells, is important on respiratory innate immunity and anti-inflammation. The action of SP-D in these diseases is still unrevealed. In this study, we used bleomycin to induce the animal model of ALI and IPF. Bleomycin is a chemotherapeutic antibiotic drug clinically used in lymphoma and squamous cell carcinomas, but the following overproduction of reactive oxygen can lead to irreversible lung injury. In this animal model, we have found that 14-day-course was the group presenting the most severe resistance and the poorest elastance of lung tissue. In addition, the pro-inflammatory cytokines (interleukin-6, interleukin-17, tumor necrosis factor-α, interferon-γ and nitric oxide) were followed by increased expression of pro-fibrotic cytokines (transforming growth factor-β1). The histological alterations caused by bleomycin such as mural incorporation of collagen and obliteration of the alveolar space are similar to human IPF. In ex vivo study, pretreatment with recombinant human SP-D or native SP-D can significantly decrease the production of pro-inflammatory cytokines. In in vivo study, treatment with native SP-D in bleomycin-induced lung fibrosis in mice also showed significant body weight increase, recovery of lung function, decline of the production of transforming growth factor-β1 (TGF-β1) and nitric oxide. Therefore, we conclude that SP-D may have prominent anti-inflammatory and anti-fibrotic effects on ALI and IPF, and also have the potential to become a novel treatment of ALI and IPF in the near future.