Rina Takamiya1, Motoko Takahashi2, Toshitaka Maeno3, Atsushi Saito4, Masaki Kato5, Takahiro Shibata6, Koji Uchida7, Shigeru Ariki2, Miyako Nakano8. 1. Department of Biochemistry, Sapporo Medical University, School of Medicine, Hokkaido, Japan. Electronic address: trina@sapmed.ac.jp. 2. Department of Biochemistry, Sapporo Medical University, School of Medicine, Hokkaido, Japan. 3. Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. 4. Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. 5. Data Knowledge Organization Unit, Head Office for Information Systems and Cybersecurity, RIKEN, Wako, Saitama, Japan. 6. Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, Japan. 7. Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan. 8. Graduate School of Integrated Sciences for Life, Hiroshima University, Higashihiroshima, Hiroshima, Japan.
Abstract
BACKGROUND: Surfactant proteins (SP) A and D belong to collectin family proteins, which play important roles in innate immune response in the lung. We previously demonstrated that cigarette smoke (CS) increases the acrolein modification of SP-A, thereby impairing the innate immune abilities of this protein. In this study, we focused on the effects of CS and its component, acrolein, on the innate immunity role of another collectin, SP-D. METHODS: To determine whether aldehyde directly affects SP-D, we examined the lungs of mice exposed to CS for 1 week and detected aldehyde-modified SP-D using an aldehyde reactive probe. The structural changes in CS extract (CSE) or acrolein-exposed recombinant human (h)SP-D were determined by western blot, liquid chromatography-electrospray ionization tandem mass spectrometry, and blue native-polyacrylamide gel electrophoresis analyses. Innate immune functions of SP-D were determined by bacteria growth and macrophage phagocytosis. RESULTS: Aldehyde-modified SP-D as well as SP-A was detected in the lungs of mice exposed to CS for 1 week. Exposure of hSP-D to CSE or acrolein induced an increased higher-molecular -weight of hSP-D and acrolein induced modification of five lysine residues in hSP-D. These modifications led to disruption of the multimer structure of SP-D and attenuated its ability to inhibit bacterial growth and activate macrophage phagocytosis. CONCLUSION: CS induced acrolein modification in SP-D, which in turn induced structural and functional defects in SP-D. GENERAL SIGNIFICANCE: These results suggest that CS-induced structural and functional defects in SP-D contribute to the dysfunction of innate immune responses in the lung following CS exposure.
BACKGROUND:Surfactant proteins (SP) A and D belong to collectin family proteins, which play important roles in innate immune response in the lung. We previously demonstrated that cigarette smoke (CS) increases the acrolein modification of SP-A, thereby impairing the innate immune abilities of this protein. In this study, we focused on the effects of CS and its component, acrolein, on the innate immunity role of another collectin, SP-D. METHODS: To determine whether aldehyde directly affects SP-D, we examined the lungs of mice exposed to CS for 1 week and detected aldehyde-modified SP-D using an aldehyde reactive probe. The structural changes in CS extract (CSE) or acrolein-exposed recombinant human (h)SP-D were determined by western blot, liquid chromatography-electrospray ionization tandem mass spectrometry, and blue native-polyacrylamide gel electrophoresis analyses. Innate immune functions of SP-D were determined by bacteria growth and macrophage phagocytosis. RESULTS:Aldehyde-modified SP-D as well as SP-A was detected in the lungs of mice exposed to CS for 1 week. Exposure of hSP-D to CSE or acrolein induced an increased higher-molecular -weight of hSP-D and acrolein induced modification of five lysine residues in hSP-D. These modifications led to disruption of the multimer structure of SP-D and attenuated its ability to inhibit bacterial growth and activate macrophage phagocytosis. CONCLUSION:CS induced acrolein modification in SP-D, which in turn induced structural and functional defects in SP-D. GENERAL SIGNIFICANCE: These results suggest that CS-induced structural and functional defects in SP-D contribute to the dysfunction of innate immune responses in the lung following CS exposure.
Authors: Claire G Nissen; Deanna D Mosley; Kusum K Kharbanda; Dawn M Katafiasz; Kristina L Bailey; Todd A Wyatt Journal: Front Immunol Date: 2022-05-20 Impact factor: 8.786