PT  - JOURNAL ARTICLE
AU  - Michael Beers
AU  - Deepika Jain
AU  - Fabian Blank
AU  - Yaniv Tomer
AU  - Christophe von Garnier
TI  - Surfactant protein D is critical for local immunomodulation in the distal lung
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p3886
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p3886.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p3886.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Surfactant Protein D (SP-D) is a multifunctional product of lung epithelia that modulates pulmonary host defense. SP-D deficient mice (SP-DKO) develop a progressive baseline phenotype of pulmonary inflammation, enhanced oxidative-nitrative stress, and lung remodeling punctuated by a morphologically heterogeneous population of mononuclear alveolar cells and poor clearance of pathogens. To further define the role of SP-D as a local modulator of this immune cell population, bronchoalveolar lavage (BAL) cells recovered from SP-DKO and C57/BL6 controls (WT) were characterized using FACS, qRT-PCR, and functional assays. By FACS, over 95% of BAL cells from WT mice consisted of a morphologically homogeneous population (FSC/SSC) with an expression profile of F4/80+, CD11c+, Dectin-1+, CD45+, CD3-, LY6G- consistent with alveolar macrophages. In contrast, SP-DKO BAL cells exhibited a dispersed FSC/SSC profile which separated into 2 major populations: Approximately 50% were F4/80+, CD11c+, Dectin-1+, CD45+ while a second group was F4/80-,CD11c-,CD45-,PECAM-, and c-Kit-. Less than 10% of the second population expressed CD3, Ly6G or CD11b. By qRT-PCR, when normalized to F4/80, BAL cells from SPDKO expressed greater amounts of iNOS and Cox2. Functionally F4/80+ SP-DKO cells internalized significantly less zymosan particulate than F4/80+ WT cells. SPDKO BAL cells in culture were hyporesponsive to stimulation by LPS and zymosan. In vivo, SP-DKO mice produced less TNF-α in response to intratracheal zymosan or LPS. These data are supportive of a critical role for SP-D in modulation of the local immune response in the lung through effects on antigen-presenting cell differentiation, composition, and function.