Abstract

and specific aims): The results from a large number of different experiments with SP-A and SP-D (lung collectins) in vitro suggest these two related proteins participate in at least two major physiologic processes: first, the regulation of lung surfactant homeostasis; and second, the non-specific innate immune response of the lung. The general objective of this project is to establish the physiological consequences of a deficiency in SP-A, SP-D or both proteins in mice to further our understanding of collectin function in the intact animal in health and disease.
The specific aims are to: 1) generate mouse models of pulmonary collectin (SP-A and SP-D) deficiency by consecutive gene disruptions of the collectin locus; 2) characterize pulmonary mechanics and surfactant structure, function and extracellular metabolism in collectin deficient mice a) under normal, non-stressed conditions, b) during exercise, c) with protein-rich pulmonary edema and d) after reversing the phosphatidylglycerol to phosphatidylinositol (PG/PI) ratio in the surfactant phospholipids; and 3) determine if pulmonary collectin deficiency a) alters the susceptibility to spontaneous respiratory infection and b) increases the susceptibility to influenza A viral infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058047-03
Application #
6030807
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1997-07-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Mun, James J; Tam, Connie; Kowbel, David et al. (2009) Clearance of Pseudomonas aeruginosa from a healthy ocular surface involves surfactant protein D and is compromised by bacterial elastase in a murine null-infection model. Infect Immun 77:2392-8
Ni, Minjian; Tam, Connie; Verma, Amrisha et al. (2008) Expression of surfactant protein D in human corneal epithelial cells is upregulated by Pseudomonas aeruginosa. FEMS Immunol Med Microbiol 54:177-84
Vigerust, David J; Ulett, Kimberly B; Boyd, Kelli L et al. (2007) N-linked glycosylation attenuates H3N2 influenza viruses. J Virol 81:8593-600
Giannoni, Eric; Sawa, Teiji; Allen, Lennell et al. (2006) Surfactant proteins A and D enhance pulmonary clearance of Pseudomonas aeruginosa. Am J Respir Cell Mol Biol 34:704-10
Casey, John; Kaplan, Jennifer; Atochina-Vasserman, Elena N et al. (2005) Alveolar surfactant protein D content modulates bleomycin-induced lung injury. Am J Respir Crit Care Med 172:869-77
Jung, Anja; Allen, Lennell; Nyengaard, Jens R et al. (2005) Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice. Anat Rec A Discov Mol Cell Evol Biol 286:885-90
Palaniyar, Nades; Clark, Howard; Nadesalingam, Jeya et al. (2005) Innate immune collectin surfactant protein D enhances the clearance of DNA by macrophages and minimizes anti-DNA antibody generation. J Immunol 174:7352-8
Atochina, Elena N; Beck, James M; Preston, Angela M et al. (2004) Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice: attenuation of cytokine responses and reactive oxygen-nitrogen species. Infect Immun 72:6002-11
Atochina, Elena N; Gow, Andrew J; Beck, James M et al. (2004) Delayed clearance of pneumocystis carinii infection, increased inflammation, and altered nitric oxide metabolism in lungs of surfactant protein-D knockout mice. J Infect Dis 189:1528-39
Hawgood, Samuel; Brown, Cynthia; Edmondson, Jess et al. (2004) Pulmonary collectins modulate strain-specific influenza a virus infection and host responses. J Virol 78:8565-72

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