Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice

Rizwanul Haque, Todd M. Umstead, Padmavathi Ponnuru, Xiaoxuan Guo, Samuel Hawgood, David Phelps, Joanna Floros

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of tissue damage. We tested the hypothesis that the lungs of SP-A(-/-) (KO) mice are more susceptible to ozone-induced damage. We compared the effects of ozone on KO and wild type (WT) mice on the C57BL/6 genetic background by exposing them to 2 parts/million of ozone for 3 or 6 h and sacrificing them 0, 4, and 24 h later. Lungs were subject to bronchoalveolar lavage (BAL) or used to measure endpoints of oxidative stress and inflammation. Despite more total protein in BAL of KO mice after a 3 h ozone exposure, WT mice had increased oxidation of protein and had oxidized SP-A dimers. In KO mice there was epithelial damage as assessed by increased LDH activity and there was increased phospholipid content. In WT mice there were more BAL PMNs and elevated macrophage inflammatory protein (MIP)-2 and monocyte chemoattractant protein (MCP)-1. Changes in MIP-2 and MCP-1 were observed in both KO and WT, however mRNA levels differed. In KO mice MIP-2 mRNA levels changed little with ozone, but in WT levels they were significantly increased. In summary, several aspects of the inflammatory response differ between WT and KO mice. These in vivo findings appear to implicate SP-A in regulating inflammation and limiting epithelial damage in response to ozone exposure.

Original languageEnglish (US)
Pages (from-to)72-82
Number of pages11
JournalToxicology and Applied Pharmacology
Volume220
Issue number1
DOIs
StatePublished - Apr 1 2007

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Pulmonary Surfactant-Associated Protein A
Ozone
Lung Injury
Chemokine CXCL2
Bronchoalveolar Lavage
Inflammation
Chemokine CCL2
Lung
Pulmonary Surfactant-Associated Proteins
Messenger RNA
Oxidative stress
Inbred C57BL Mouse
Dimers
Phospholipids
Pneumonia
Proteins
Oxidative Stress
Repair
Asthma
Tissue

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

Haque, Rizwanul ; Umstead, Todd M. ; Ponnuru, Padmavathi ; Guo, Xiaoxuan ; Hawgood, Samuel ; Phelps, David ; Floros, Joanna. / Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice. In: Toxicology and Applied Pharmacology. 2007 ; Vol. 220, No. 1. pp. 72-82.
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Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice. / Haque, Rizwanul; Umstead, Todd M.; Ponnuru, Padmavathi; Guo, Xiaoxuan; Hawgood, Samuel; Phelps, David; Floros, Joanna.

In: Toxicology and Applied Pharmacology, Vol. 220, No. 1, 01.04.2007, p. 72-82.

Research output: Contribution to journalArticle

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T1 - Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice

AU - Haque, Rizwanul

AU - Umstead, Todd M.

AU - Ponnuru, Padmavathi

AU - Guo, Xiaoxuan

AU - Hawgood, Samuel

AU - Phelps, David

AU - Floros, Joanna

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N2 - Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of tissue damage. We tested the hypothesis that the lungs of SP-A(-/-) (KO) mice are more susceptible to ozone-induced damage. We compared the effects of ozone on KO and wild type (WT) mice on the C57BL/6 genetic background by exposing them to 2 parts/million of ozone for 3 or 6 h and sacrificing them 0, 4, and 24 h later. Lungs were subject to bronchoalveolar lavage (BAL) or used to measure endpoints of oxidative stress and inflammation. Despite more total protein in BAL of KO mice after a 3 h ozone exposure, WT mice had increased oxidation of protein and had oxidized SP-A dimers. In KO mice there was epithelial damage as assessed by increased LDH activity and there was increased phospholipid content. In WT mice there were more BAL PMNs and elevated macrophage inflammatory protein (MIP)-2 and monocyte chemoattractant protein (MCP)-1. Changes in MIP-2 and MCP-1 were observed in both KO and WT, however mRNA levels differed. In KO mice MIP-2 mRNA levels changed little with ozone, but in WT levels they were significantly increased. In summary, several aspects of the inflammatory response differ between WT and KO mice. These in vivo findings appear to implicate SP-A in regulating inflammation and limiting epithelial damage in response to ozone exposure.

AB - Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of tissue damage. We tested the hypothesis that the lungs of SP-A(-/-) (KO) mice are more susceptible to ozone-induced damage. We compared the effects of ozone on KO and wild type (WT) mice on the C57BL/6 genetic background by exposing them to 2 parts/million of ozone for 3 or 6 h and sacrificing them 0, 4, and 24 h later. Lungs were subject to bronchoalveolar lavage (BAL) or used to measure endpoints of oxidative stress and inflammation. Despite more total protein in BAL of KO mice after a 3 h ozone exposure, WT mice had increased oxidation of protein and had oxidized SP-A dimers. In KO mice there was epithelial damage as assessed by increased LDH activity and there was increased phospholipid content. In WT mice there were more BAL PMNs and elevated macrophage inflammatory protein (MIP)-2 and monocyte chemoattractant protein (MCP)-1. Changes in MIP-2 and MCP-1 were observed in both KO and WT, however mRNA levels differed. In KO mice MIP-2 mRNA levels changed little with ozone, but in WT levels they were significantly increased. In summary, several aspects of the inflammatory response differ between WT and KO mice. These in vivo findings appear to implicate SP-A in regulating inflammation and limiting epithelial damage in response to ozone exposure.

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