0
Articles |

Protease Injury in the Development of COPD*: Thomas A. Neff Lecture

Harold A. Chapman, Jr., MD; Guo-Ping Shi, DSc
Author and Funding Information

*From the Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA.

Correspondence to: Harold A. Chapman, Jr., MD, Respiratory Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115; e-mail: hchapman@rics.bwh.harvard.edu



Chest. 2000;117(5_suppl_1):295S-299S. doi:10.1378/chest.117.5_suppl_1.295S
Text Size: A A A
Published online

Extract

Abbreviations: AAT = α1-antitrypsin; MME = macrophage metalloelastase; SMC = smooth muscle cells

Proteases are a class of hydrolytic enzymes mediating irreversible disruption of protein amide bonds. Based on the key amino acids used by proteases to attack the targeted bond, these enzymes are commonly classified into four distinct groups: serine, metallo, aspartate, and cysteine.1 Proteolysis mediated by these enzymes is vital to many aspects of normal cell function, including regulation of the interface between cells and the extracellular matrices in which they reside. And yet, unchecked extracellular proteolytic activity is linked to excessive destruction of extracellular matrices and untoward clinical events such as bleeding, joint destruction, and osteoporosis.24 Since the discovery that deficiency of a serine protease inhibitor, α1-antitrypsin (AAT), is a cause of panlobular lung destruction, the pathogenesis of emphysema has been strongly linked to the excessive action of proteolytic enzymes.5 This discovery prompted the widespread belief that COPD, and smokers’ emphysema in particular, is due to excessive activity of the major serine protease inhibited by AAT, neutrophil elastase. However numerous attempts in the ensuing 35 years to prove this hypothesis has instead left considerable doubt as to the role of neutrophil elastase and possibly proteases in general in the development of smokers’ emphysema. This discussion will attempt to provide a current perspective on the role of proteases in the pathogenesis of COPD.

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