HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Cathepsin L protects mice from mycoplasmal infection and is essential for airway lymphangiogenesis.

Abstract
Cathepsin L (Ctsl) is a proposed therapeutic target to control inflammatory responses in a number of disease states. However, Ctsl is thought to support host defense via its involvement in antigen presentation pathways. Hypothesizing that Ctsl helps combat bacterial infection, we investigated its role in Mycoplasma pulmonis-infected mice as a model of acute and chronic infectious airway inflammation. Responses to the airway inoculation of mycoplasma were compared in Ctsl(-/-) and Ctsl(+/+) mice. After infection, Ctsl(-/-) mice demonstrated more body weight loss, greater mortality (22% versus 0%, respectively), and heavier lungs than Ctsl(+/+) mice, but had smaller bronchial lymph nodes. The burden of live mycoplasma in lungs was 247-fold greater in Ctsl(-/-) mice than in Ctsl(+/+) mice after infection for 3 days. Ctsl(-/-) mice exhibited more severe pneumonia and neutrophil-rich, airway-occlusive exudates, which developed more rapidly than in Ctsl(+/+) mice. Compared with the conspicuous remodeling of lymphatics after infection in Ctsl(+/+) mice, little lymphangiogenesis occurred in Ctsl(-/-) mice, but blood vessel remodeling and tissue inflammation were similarly severe. Titers of mycoplasma-reactive IgM, IgA, and IgG in blood in response to live and heat-killed organisms were similar to those in Ctsl(+/+) mice. However, enzyme-linked immunosorbent spot assays revealed profound reductions in the cellular IFN-γ response to mycoplasma antigen. These findings suggest that Ctsl helps contain mycoplasma infection by supporting lymphangiogenesis and cellular immune responses to infection, and our findings predict that the therapeutic inhibition of Ctsl could increase the severity of mycoplasmal infections.
AuthorsXiang Xu, John Greenland, Peter Baluk, Alicia Adams, Oishee Bose, Donald M McDonald, George H Caughey
JournalAmerican journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 49 Issue 3 Pg. 437-44 (Sep 2013) ISSN: 1535-4989 [Electronic] United States
PMID23600672 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Interferon-gamma
  • Cathepsin L
  • Ctsl protein, mouse
Topics
  • Acute Disease
  • Animals
  • Antibodies, Bacterial (blood, immunology)
  • Antigens, Bacterial (blood, immunology)
  • Bacterial Load
  • Cathepsin L (deficiency, genetics, immunology)
  • Chronic Disease
  • Gene Expression (immunology)
  • Interferon-gamma (blood, immunology)
  • Lung (enzymology, immunology, microbiology)
  • Lymphangiogenesis (immunology)
  • Lymphatic Vessels (immunology)
  • Mice
  • Mycoplasma Infections (enzymology, immunology, microbiology, mortality)
  • Mycoplasma pulmonis (growth & development)
  • Severity of Illness Index
  • Survival Analysis

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: