Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice

László Hortobágyi et al. 2008. J. Allergy Clin. Immunol.

Speaker: Yu-Lun Cheng (鄭宇倫)                                         Time: 14:00~15:00, Oct. 8, 2008

Commentator: Chiou-Feng Lin, Ph.D. (林秋烽老師)     Place: Room 601

Abstract:

Surfactant protein (SP) plays an important role in local immune in the lung. SP can help to clean the pathogens and to modulate innate immune cells (1). The effects of SPs on alveolar macrophages are controversial because previous studies showed that SPs stimulated (2) and inhibited (3)proinflammatory functions, including TNF-α production. But the mechanism how SP affect the inflammation of the lung through TNF-α is still unclear. Authors hypothesized that both of TNF-α and surfactant protein D (SP-D) serve as antagonists in the regulation of antigen-presenting cells in the lung. The results showed that the expression of TNF-α in the airways was associated with enhanced production of SP-D. Next, authors attempted to know whether TNF-α can direct regulate SP-D synthesis. In vitro experiments, addition of TNF-α (up to 100 ng) to type II alveolar epithelial cells did not alter SP-D levels recovered in the culture. Besides, in both allergen challenge model and TNF-α over-expression model, high level of TNF-α was associated with IL-13 mRNA activation. Then, the cell count, morphology, and activation of CD11c⁺ cells were abnormal in the bronchoalveolar lavage fluid (BAL fluid) of SP-D^-/- mice. In addition, authors further discovered that CD11c was diminished by internalization of membrane molecules in SP-D^-/- mice. Compared with these cells of wild type mice, CD11c⁺ cells in the BAL cells of SP-D^-/- mice expressed high level of CD86 and CD11b surface molecules. In other words, in addition to macrophages, the presence of activated myeloid dendritic cells was in the BAL fluid of SP-D^-/- mice. Therefore, authors confirmed that the lack of SP-D enhanced TNF-α expression in CD11c⁺ cells. By bone marrow derived dendritic cells treated with recombinant mouse SP-D, the expression of MHC class II, CD86, and CD11b were significantly inhibited. Summarized of all, TNF-α is important not only to initiate pro-inflammation but also to regulate anti-inflammation by enhancing production of SP-D. SoTNF-α and SP-D are significant for negative feedback regulation of acute inflammatory responses in the respiratory tract. Further, TNF-α and SP-D maybe enable to prevent the development of chronic conditions, such as asthma.

References:

1.     Pastva, A. M. et al. 2007. Immunomodulatory roles of surfactant proteins A and D: implications in lung disease.         Proc. Am. Thorac. Soc. 4: 252-257.

2.     Weikert, L. F. et al. 2000. Surfactant protein A enhances mycobacterial killing by rat macrophages through a nitric oxide-dependent pathway. Am J Physiol Lung Cell Mol Physiol 279: 216-223.

3.     McIntosh, J. C. et al. 1996. Surfactant protein A protects growing cells and reduces TNF-alpha activity from LPS-stimulated macrophages. Am J Physiol Lung Cell Mol Physiol 271: 310-319.