한빛사 논문
Geon Ho Bae 1, Ye Seon Kim 1, Ji Ye Park 1, Mingyu Lee 2, Sung Kyun Lee 3, Ji Cheol Kim 1, Jang Gyu Kim 1, Ye Ji Shin 1, Ho Lee 4, Soo-Youl Kim 5, Yong-Soo Bae 1, Brian A Zabel 6, Hong Sook Kim 1, Yoe-Sik Bae 1 2
1Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
3Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
4Graduate School of Cancer Science and Policy and.
5Research Institute, Division of Cancer Biology, National Cancer Center, Goyang, Republic of Korea; and.
6Palo Alto Veterans Institute for Research, Veterans Affairs Hospital, Palo Alto, CA.
*Corresponding author.
Abstract
Lung-resident neutrophils need to be tightly regulated to avoid degranulation- and cytokine-associated damage to fragile alveolar structures that can lead to fatal outcomes. Here we show that lung neutrophils (LNs) express distinct surface proteins and genes that distinguish LNs from bone marrow and blood neutrophils. Functionally, LNs show impaired migratory activity toward chemoattractants and produce high levels of interleukin-6 (IL-6) at steady state and low levels of tumor necrosis factor-α in response to lipopolysaccharide (LPS) challenge. Treating bone marrow neutrophils with bronchoalveolar lavage fluid or prostaglandin E2 induces LN-associated characteristics, including the expression of transglutaminase 2 (Tgm2) and reduced production of inflammatory cytokines upon LPS challenge. Neutrophils from Tgm2−/− mice release high levels of inflammatory cytokines in response to LPS. Lung damage is significantly exacerbated in Tgm2−/− mice in an LPS-induced acute respiratory distress syndrome model. Collectively, we demonstrate that prostaglandin E2 is a key factor for the generation of LNs with unique immune suppressive characteristics, acting through protein kinase A and Tgm2, and LNs play essential roles in protection of the lungs against pathogenic inflammation.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기