0
Articles |

Spontaneous Emphysema in Surfactant Protein D Gene-Targeted Mice*

Susan Wert, PhD; Tracy Jones; Thomas Korfhagen, MD; James Fisher, MD, FCCP; Jeffrey Whitsett, MD
Author and Funding Information

*From the Children’s Hospital Medical Center, Cincinnati, OH, and University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Susan Wert, PhD, Division of Pulmonary Biology, Children’s Hospital Medical Center/Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229-2029; e-mail: Susan.Wert@CHMCC.org.



Chest. 2000;117(5_suppl_1):248S. doi:10.1378/chest.117.5_suppl_1.248S
Text Size: A A A
Published online

Extract

Abbreviation: SP-D = surfactant protein D

Surfactant protein D (SP-D), a 43-kDa member of the collectin family of innate defense molecules, is expressed primarily in the respiratory epithelium. Targeted deletion of the SP-D gene resulted in pulmonary lipoidosis and accumulation of lipid-laden alveolar macrophages in the lungs of SP-D (−/−) mice by 8 to 12 wk of age.1 Histopathological findings at 6 mo of age consisted of enlarged airspaces with multiple focal areas of macrophage accumulation, and perivascular/peribronchiolar monocytic infiltrates. Mice were maintained in pathogen-free conditions and there was no serologic evidence of viral infection. To characterize the role of SP-D in alveolar formation or enlargement, morphometric analysis of the lungs of SP-D (−/−) mice was performed at 5 days, 14 days, 3 weeks, 6 weeks, and 7 months of age. Three to five SP-D (−/−) mice and SP-D (+/+) controls were sacrificed at each time point; the lungs were inflation-fixed with 4% paraformaldehyde in phosphate-buffered saline, at a pressure of 25 cm H2O. There were no significant differences in body weights, lung volumes, or lung volume to body weight ratios between the SP-D (−/−) mice and age-matched SP-D (+/+) controls. Morphometric measurements were performed on paraffin sections to determine the proportion (percentage of fractional area) of respiratory parenchyma and airspace at each time point. No abnormalities were observed between 5 and 14 days of age, ie, during transition from the saccular to the alveolar stage of lung development. Enlarged airspaces were readily apparent, however, by 3 weeks of age, and they increased in size thereafter. The relative proportion of airspace in the SP-D (−/−) mice increased significantly by 7 months of age, while that of the respiratory parenchyma decreased, compared to SP-D (+/+) controls. At 7 months, the percentage of fractional area for airspace was 68.7% (SP-D −/−) vs 54.0% (SP-D +/+); for the respiratory parenchyma, it was 31.3% (SP-D −/−) vs 45.9% (SP-D +/+) (p = 0.004). Abnormalities in both collagen and elastin staining were also observed. These findings were associated with accumulation of peribronchiolar and subpleural alveolar macrophage infiltrates. SP-D deficiency caused progressive enlargement of pulmonary acini consistent with the development of emphysema. These results demonstrate a previously unknown role for SP-D in the regulation of inflammation and pulmonary remodeling in vivo.

First Page Preview

View Large
First page PDF preview

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543