0
Articles |

Extracellular Matrix Remodeling in Idiopathic Pulmonary Fibrosis*

Annie Pardo, PhD; Moisés Selman, MD, FCCP
Author and Funding Information

*From the Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.

Correspondence to: Annie Pardo, PhD, Faculty of Sciences, Universidad Nacional Autonoma de Mexico, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, CP 14080, México DF, México.



Chest. 2001;120(1_suppl):S77. doi:10.1378/chest.120.1_suppl.S77
Text Size: A A A
Published online

Extract

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disorder characterized by fibroblast proliferation and extracellular matrix accumulation. The molecular mechanisms behind the aberrant tissue remodeling should involve the families of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs), main mediators of extracellular matrix turnover. We evaluated by immunohistochemistry and in situ hybridization, the presence of collagenases 1, 2, and 3, gelatinases A and B, membrane type (MT)1-MMP, and TIMPs 1, 2, 3, and 4, in 12 IPF lungs and 6 control lungs. Collagenase-1 was localized in alveolar macrophages and type 2 pneumocytes, mainly those lining honeycomb cysts. Collagenase-2 was observed in neutrophils, and collagenase-3 was not detected, even when assayed by reverse transcriptase-polymerase chain reaction. Gelatinase A was noticed in myofibroblasts close to areas of basement membrane disruption. MT1-MMP was observed in widely spaced interstitial cells and in alveolar epithelial cells. Gelatinase B was found in neutrophils and alveolar epithelial cells and, interestingly, in myofibroblasts foci, a finding corroborated in vitro by reverse transcriptase-polymerase chain reaction. TIMP-1 was present in interstitial macrophages and fibroblasts in areas of dense scar tissue, while TIMP-2 was found in myofibroblast. TIMP-3 was localized mainly coupled to the elastic lamina of vessels, revealing the characteristic duplication of this structure in pulmonary fibrosis. TIMP-4 was expressed by alveolar epithelial and plasma cells. These findings suggest that in IPF (1) there is a higher expression of TIMPs compared with collagenases in the lung parenchyma, suggesting that a nondegrading fibrillar collagen microenvironment is prevailing; and (2) excessive gelatinases production might play a role in basement membrane disruption, enhancing fibroblast invasion to the alveolar spaces.

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