US EPA

2266842 

Journal Article 

Abstract 

In a model of innate immunity the interaction between inducible nitric oxide synthase and surfactant protein-A regulates airway responsiveness 

Pastva, AM; Walker, JKL; Mukherjee, S; Giamberardino, C; Hsia, BJ; Potts, E; Eu, JP; Foster, WM; Que, LG; Wright, JR, JR 

2010 

Yes 

American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 

181 

A2455 

English 

10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A2455 

WOS:000208771001369 

is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans

Rationale: Surfactant-associated protein (SP)-A is a member of the collectin family of innate immune effector proteins and is an integral component of the pulmonary host defense system. SP-A has been shown to modulate immune responses to endotoxin, or lipopolysaccharide (LPS), the major cell wall component of gram-negative bacteria. Exposure to LPS contributes substantially to the pathophysiology of a variety of lung diseases. Previously, we reported that following exposure to LPS SP-A null mice had reduced airway hyperresponsiveness (AHR) as compared to WT (wild-type) mice although both WT and SP-A nulls had similar levels of lung inflammation (Maddox et al., Am. J. Respir. Crit. Care Med., Apr 2003;167). To further study the mechanism of the reduced AHR we investigated the interaction of SP-A with nitric oxide, a potent bronchodilator.

Methods: Mice were exposed to either aerosolized saline or LPS for 2 h. Between 4 to 6 h after the initiation of the aerosol exposure, mice were either assessed in vivo for AHR using the forced oscillation technique or euthanized for tissue harvest.

Results: The LPS-exposed SP-A null mice had comparable inflammatory indices (i.e., cell counts, cytokines levels) but attenuated AHR compared to their WT counterparts. We further established that the attenuation of AHR was not dependent upon SP-D expression levels or airway smooth muscle physiological properties since these measures were similar between WT and SP-A null mice. We then made the novel observation that the lungs from LPS-treated SP-A null mice had elevated inducible nitric oxide synthase (iNOS) expression along with elevated nitrite levels. In addition, when SP-A null mice were pre-treated with the iNOS specific inhibitor 1400W and exposed to LPS, the attenuation of AHR was completely abrogated. Thus, the interaction between SP-A and iNOS is a controlling factor in the regulation of LPS-induced airway responsiveness.

Conclusion: Taken together, our new data suggest that in models of innate immunity SP-A plays an integral role, and if deficient, physiological function of the airway remains intact despite robust inflammatory responses. These results have potential impact in clinical settings where SP-A sufficiency may be called into question, i.e., cystic fibrosis, acute lung injury, and asthma. 

American Thoracic Society 2010 International Conference 

New Orleans, LA 

May 14-19, 2010