Effect of insulin-like growth factor blockade on hyperoxia-induced lung injury.

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.

• Authors: Tae-Hyung Kim, Yu-Hua Chow, Sean E Gill, Lynn M Schnapp
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 47 Issue 3 Pg. 372-8 (Sep 2012) ISSN: 1535-4989 [Electronic] United States
• PMID: 22493012 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Somatomedins

Topics

• Animals
• Bronchoalveolar Lavage Fluid
• Chemotaxis, Leukocyte
• Cytokines (metabolism)
• Female
• Hyperoxia (complications)
• Lung Injury (etiology, metabolism)
• Mice
• Mice, Inbred C57BL
• Somatomedins (antagonists & inhibitors, metabolism)