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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL058047-01
Application #
2031260
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1997-07-01
Project End
2001-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
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
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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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