Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice.
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.
Haque
Rizwanul
R
Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Umstead
Todd M
TM
Ponnuru
Padmavathi
P
Guo
Xiaoxuan
X
Hawgood
Samuel
S
Phelps
David S
DS
Floros
Joanna
J
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000633:toxicity*; D010743:Phospholipids / Q000032:analysis; D011506:Proteins / Q000032:analysis; D037662:Pulmonary Surfactant-Associated Protein A / Q000502:physiology*
D016207:Cytokines; D010743:Phospholipids; D011506:Proteins; D037662:Pulmonary Surfactant-Associated Protein A; D010126:Ozone; D007770:L-Lactate Dehydrogenase; D005978:Glutathione