Acrolein in cigarette smoke attenuates the innate immune responses mediated by surfactant protein D

• Published in: Biochimica et biophysica acta. General subjects Vol. 1864; no. 11; p. 129699
• Main Authors: Takamiya, Rina, Takahashi, Motoko, Maeno, Toshitaka, Saito, Atsushi, Kato, Masaki, Shibata, Takahiro, Uchida, Koji, Ariki, Shigeru, Nakano, Miyako
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2020
• Subjects: Acrolein; Acrolein - adverse effects; Acrolein - analysis; Animals; bacterial growth; Cigarette smoke; cigarettes; electrospray ionization mass spectrometry; Female; gel electrophoresis; Humans; immune response; Immunity, Innate - drug effects; Innate immunity; liquid chromatography; Lung - drug effects; Lung - immunology; lungs; lysine; macrophages; Mice; Mice, Inbred C57BL; Nicotiana - chemistry; Phagocytosis - drug effects; Pulmonary surfactant protein; Pulmonary Surfactant-Associated Protein D - analysis; Pulmonary Surfactant-Associated Protein D - immunology; Recombinant Proteins - analysis; Recombinant Proteins - immunology; smoke; Smoke - adverse effects; Smoke - analysis; SP-D; surfactant proteins; tandem mass spectrometry; Tobacco Smoking - adverse effects; Tobacco Smoking - immunology; Western blotting; PBS; BN-PAGE; Pulmonary surfactant protein; Innate immunity; EDTA; CS; Acrolein; SDS-PAGE; SP-D; CRD; CSE; IAM; SP; Cigarette smoke; COPD; ARP
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2020.129699

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. 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. 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. CS induced acrolein modification in SP-D, which in turn induced structural and functional defects in SP-D. 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. •Aldehyde-modified SP-D was observed in 1-week cigarette smoke (CS)-exposed lung.•Exposure to CS extracts induced acrolein modification of human SP-D.•Acrolein-modfied sites were located in CRD, especially at the short loop.•Acrolein disrupted the multimer structure of SP-D.•CS decreased the abilities of SP-D to mediate the innate immune response.