Chest ACCP Member Benefits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Girod, C.E.
Right arrow Articles by Miller, Y.E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Girod, C.E.
Right arrow Articles by Miller, Y.E.
(Chest. 1999;116:61S.)
© 1999 American College of Chest Physicians

Surfactant Protein C Promoter-Driven Expression of T1-Alpha Induces Lung Inflammation*

C.E. Girod, MD; D.H. Shin, MD, FCCP; M.W. Geraci, MD; H.B. Warren; L.G. Dobbs, MD, FCCP; B. Gao; J.S. Rainer; A.K. Bauer; M. Ikegami; J.M. Shannon, PhD and Y.E. Miller, MD

* From the Veterans Affairs Medical Center, University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: M.W. Geraci, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, 4200 E Ninth Ave, Denver, CO 80262

T1-alpha (TIA) is a cell membrane protein expressed with high specificity by the alveolar (primarily type I cell), choroid plexus, and ciliary (ocular) epithelia in the rat. In the lung, TIA undergoes upregulation prior to birth as well as in several models of lung injury. The unusual pattern of basal expression and upregulation with physiologically critical events supports an important function for TIA. Analysis of predicted protein structure suggests that TIA is a type Ia membrane glycoprotein, but no homologies or motifs provide clues to function.

As one approach to determine function, we have expressed both the intact rat TIA (DT900) and a deletion mutant (DT600) lacking the transmembrane helix and short cytoplasmic tail under the control of the human surfactant protein C (SPC) promoter in FVB/N mice. DT900 transgenics exhibit intra-alveolar accumulation of macrophages as well as perivascular accumulation of mononuclear cells, compared with nontransgenic littermates (7/8 vs 1/7, p = 0.01). Immunohistochemistry reveals close apposition between alveolar macrophages and TIA expressing type II cells. DT900 transgenics have increased lung/body weight ratios compared with littermates (0.0166 vs 0.0136, p = 0.02), increased BAL macrophages (0.88 vs 0.56 x 105/mL, p = 0.06 at 6 weeks; 1.48 vs 0.84 x 105/mL, p = 0.00005 at 12 weeks), and decreased survival in 95 to 100% O2 at 630 mm Hg (2/5 vs 7/7, p = 0.05). DT900 transgenics dying of hyperoxia display diffuse pulmonary inflammatory changes, including neutrophilic infiltration involving small- and medium-sized veins and arteries. Surfactant pool size and 3H choline incorporation rates are higher in DT900 transgenics than in nontransgenic littermates. DT600 transgenics display apparently normal lung histology but have a trend toward decreased survival in 95 to 100% O2 at 630 mm Hg (2/4 vs 7/7). Surfactant pool size, 3H choline incorporation, and secretion rates are not different between DT600 transgenics and nontransgenic littermates, making a surfactant binding function for TIA unlikely. SPC promoter-driven expression of TIA may perturb type II cell function in some nonspecific fashion, leading to accumulation of macrophages. Alternatively, the overexpression of TIA in the context of the type II cell may directly cause increased macrophage accumulation, perhaps through adhesive mechanisms.




This article has been cited by other articles:


Home page
 ThoraxHome page
A J Sandford and E K Silverman
Chronic obstructive pulmonary disease * 1: Susceptibility factors for COPD the genotype-environment interaction
Thorax, August 1, 2002; 57(8): 736 - 741.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. B. KHATRI, M. OZKAN, K. MCCARTHY, D. LASKOWSKI, J. HAMMEL, R. A. DWEIK, and S. C. ERZURUM
Alterations in Exhaled Gas Profile during Allergen-induced Asthmatic Response
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1844 - 1848.
[Abstract] [Full Text] [PDF]

Home page
 NeoReviewsHome page
P. A. Dennery
The Biology of Heme Oxygenase During Development
NeoReviews, March 1, 2001; 2(3): e67 - 73.
[Full Text]

Home page
 JEMHome page
S. Brouard, L. E. Otterbein, J. Anrather, E. Tobiasch, F. H. Bach, A. M.K. Choi, and M. P. Soares
Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis
J. Exp. Med., October 2, 2000; 192(7): 1015 - 1026.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Girod, C.E.
Right arrow Articles by Miller, Y.E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Girod, C.E.
Right arrow Articles by Miller, Y.E.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS