Effect of Insulin-Like Growth Factor Blockade on Hyperoxia-Induced Lung Injury
- Authors
- Kim, Tae-Hyung; Chow, Yu-Hua; Gill, Sean E.; Schnapp, Lynn M.
- Issue Date
- Sep-2012
- Publisher
- AMER THORACIC SOC
- Keywords
- insulin-like growth factor; hyperoxia-induced lung injury; neutrophils
- Citation
- AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, v.47, no.3, pp.372 - 378
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
- Volume
- 47
- Number
- 3
- Start Page
- 372
- End Page
- 378
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/164839
- DOI
- 10.1165/rcmb.2012-0085OC
- ISSN
- 1044-1549
- Abstract
- Insulin-like growth factor (IGF)-1 is increased in different models of acute lung injury, and is an important determinant of survival and proliferation in many cells. We previously demonstrated that treatment of mice with IGF-1 receptor-blocking antibody (A12) improved early survival in bleomycin-induced lung injury. We have now examined whether administration of A12 improved markers of lung injury in hyperoxia model of lung injury. C57BL/6 mice underwent intraperitoneal administration of A12 or control antibody (keyhole limpet hemocyanin [KLH]), then were exposed to 95% hyperoxia for 88-90 hours. Mice were killed and bronchoalveolar lavage (BAL) and lung tissue were obtained for analysis. Hyperoxia caused a significant increase in IGF levels in BAL and lung lysates. Peripheral blood neutrophils expressed IGF-1R at baseline and after hyperoxia. BAL neutrophils from hyperoxia-treated mice and patients with acute lung injury also expressed cell surface IGF-1R. A12-treated mice had significantly decreased polymorphonuclear cell (PMN) count in BAL compared with KLH control mice (P = 0.02). BAL from A12-treated mice demonstrated decreased PMN chemotactic activity compared with BAL from KLH-treated mice. Pretreatment of PMNs with A12 decreased their chemotactic response to BAL from hyperoxia exposed mice. Furthermore, IGF-1 induced a dose-dependent chemotaxis of PMNs. There were no differences in other chemotactic cytokines in BAL, including CXCL1 and CXCL2. In summary, IGF blockade decreased PMN recruitment to the alveolar space in a mouse model of hyperoxia. Furthermore, the decrease in BAL PMNs was at least partially due to a direct effect of A12 on PMN chemotaxis.
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