Cigarette smoke-induced hypercapnic emphysema in C3H mice is associated with increases of macrophage metalloelastase and substance P in the lungs.
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.
Xu
J
J
Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA.
Xu
F
F
Wang
R
R
Seagrave
Jc
J
Lin
Y
Y
March
T H
TH
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002245:Carbon Dioxide / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006935:Hypercapnia / Q000209:etiology*; D000860:Hypoxia / Q000209:etiology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D053508:Matrix Metalloproteinase 12 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D010100:Oxygen / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000209:etiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018040:Receptors, Neurokinin-1; D013373:Substance P / Q000235:genetics / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D019715:Tissue Inhibitor of Metalloproteinase-1; D014028:Tobacco Smoke Pollution; D002245:Carbon Dioxide; D013373:Substance P; D053508:Matrix Metalloproteinase 12; D010100:Oxygen