Cigarette smoke-induced hypercapnic emphysema in C3H mice is associated with increases of macrophage metalloelastase and substance P in the lungs

Exp Lung Res. Jun-Jul 2007;33(5):197-215. doi: 10.1080/01902140701459514.

Abstract

The authors tested whether macrophage metalloelastase (MMP-12) and substance P (SP) were increased in the cigarette smoke (CS)-exposed female C3H/HeN mice with hypercapnic emphysema. The authors found that as compared to control (filtered air), 16 weeks of CS exposure significantly up-regulated mRNA and protein levels of MMP-12, the ratio of MMP-12/tissue inhibitor of matrix metalloproteinase-1, and SP/preprotachykinin-A (a precursor to SP) in the lungs. Importantly, a significant correlation was found between MMP-12 and SP, and between MMP-12/SP and the degrees of hypoxemia/hypercapnia denoted in CS-exposed mice. These data suggest a possible involvement of SP and MMP-12 in the pathogenesis of severe COPD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Carbon Dioxide / blood
  • Female
  • Gene Expression Regulation
  • Hypercapnia / etiology*
  • Hypoxia / etiology
  • Lung / metabolism*
  • Lung / pathology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / pathology
  • Matrix Metalloproteinase 12 / genetics
  • Matrix Metalloproteinase 12 / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Oxygen / blood
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Emphysema / etiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Neurokinin-1
  • Substance P / genetics
  • Substance P / metabolism*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tobacco Smoke Pollution / adverse effects*

Substances

  • RNA, Messenger
  • Receptors, Neurokinin-1
  • Tissue Inhibitor of Metalloproteinase-1
  • Tobacco Smoke Pollution
  • Carbon Dioxide
  • Substance P
  • Matrix Metalloproteinase 12
  • Oxygen