HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 34, 24496-24505, August 25, 2006

This Article Full Text Full Text (PDF) An addition or correction has been published All Versions of this Article: 281/34/24496    most recent M600651200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kingma, P. S. Articles by Whitsett, J. A. Search for Related Content PubMed PubMed Citation Articles by Kingma, P. S. Articles by Whitsett, J. A. Social Bookmarking                      What's this?

Correction of Pulmonary Abnormalities in Sftpd^-/- Mice Requires the Collagenous Domain of Surfactant Protein D^*

Paul S. Kingma, Liqian Zhang, Machiko Ikegami, Kevan Hartshorn, Francis X. McCormack^¶, and Jeffrey A. Whitsett¹

From the Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, Departments of Medicine and Pathology, Boston University School of Medicine, Boston, Massachusetts 02118-3393, and ^¶Pulmonary/Critical Care Division, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0564

Surfactant protein D (SP-D) is a member of the collectin family of innate defense proteins. Members of this family share four distinct structural domains: an N-terminal cross-linking domain, a collagenous domain, a neck region, and a carbohydrate recognition domain. In this study, the function of the collagenous domain was evaluated by expressing a SP-D collagen deletion mutant protein (rSftpdCDM) in wild type and SP-D null mice (Sftpd^-/-). rSftpdCDM formed disulfide-linked trimers that further oligomerized into higher order structures. The mutant protein effectively bound carbohydrate and aggregated bacteria in vitro. Whereas rSftpdCDM did not disrupt pulmonary morphology or surfactant phospholipid levels in wild type mice, the mutant protein failed to rescue the emphysema or enlarged foamy macrophages that are characteristic of Sftpd^-/- mice. Moreover, rSftpdCDM partitioned with small aggregate surfactant in a manner similar to SP-D, but rSftpdCDM did not correct the abnormal surfactant ultrastructure or phospholipid levels observed in Sftpd^-/- mice. In contrast, rSftpdCDM completely corrected viral clearance and the abnormal inflammatory response that occurs following pulmonary influenza A challenge in Sftpd^-/- mice. Our findings indicate that the collagen domain of SP-D is not required for assembly of disulfide-stabilized oligomers or the innate immune response to viral pathogens. The collagen domain of SP-D is required for the regulation of pulmonary macrophage activation, airspace remodeling, and surfactant lipid homeostasis.

Received for publication, January 23, 2006 , and in revised form, June 19, 2006.

^* This work was supported by National Institutes of Health (NIH) Grants HL56387 (to J. A. W.), HL63329 (to M. I.), and HL68861 (to F. X. M.) and NHLBI, NIH, Grant HL60931 (to K. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, 3333 Burnet Ave., Cincinnati, OH 45229-3039. Tel.: 513-636-4830; Fax: 513-636-7868; E-mail: jeff.whitsett{at}cchmc.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Ikegami, S. Grant, T. Korfhagen, R. K. Scheule, and J. A. Whitsett Surfactant protein-D regulates the postnatal maturation of pulmonary surfactant lipid pool sizes J Appl Physiol, May 1, 2009; 106(5): 1545 - 1552. [Abstract] [Full Text] [PDF]

				M. White, P. Kingma, T. Tecle, N. Kacak, B. Linders, J. Heuser, E. Crouch, and K. Hartshorn Multimerization of Surfactant Protein D, but Not Its Collagen Domain, Is Required for Antiviral and Opsonic Activities Related to Influenza Virus J. Immunol., December 1, 2008; 181(11): 7936 - 7943. [Abstract] [Full Text] [PDF]

				A. V. Andreeva, M. A. Kutuzov, and T. A. Voyno-Yasenetskaya Regulation of surfactant secretion in alveolar type II cells Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L259 - L271. [Abstract] [Full Text] [PDF]