¹Scientific Center for Children’s Health of RAM S, Moscow, Russian Federation
²Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
*Corresponding author: Еlena M. Vasilyeva PhD, ScD; Laboratory of Clinical Biochemistry, Scientific Center for Children’s Health of Russian Academy of Medical Sciences, 2/62, Lomonosov ave., Moscow, 117963, Russia. Tel: 7-499-1254954. E-mail: Elenafirstname.lastname@example.org
In the lung, the pathogenesis of emphysema (Em) is complicated and involves several endogenous factors: protease-antiprotease imbalance, α1-antitrypsin deficiency, oxidative stress (OS), and ion imbalance. It is our contention that an increase in the free Fe level in combination with a significant decrease of SOD activity that we detected is disadvantageous for patients with lung pathology, particularly in cases with complicated Em. GP and SOD activity decrease in patients with Em. The Zn/Cu ratio also decreases during Em, whereas the Zn in/Cu ratio is increased, when compared with patients without Em. We discovered the activation of HNE (not distinctively expressed, but obviously, prolonged over time), and have assumed an increase in cathepsin G activity (according to antiG activation). A moderate rise in the MMP-7 level can indicate an inactivation of the remodeling processes in these patients, and a part of the compensatory mechanisms. This assumption is confirmed by the MMP-7 correlation links found in cases of Em, with anti-NE and anti-G activity (r=+0.67 and r=+0.64, correspondingly) that the use of antioxidants alone has little effect, as these drugs cannot neutralize the main chain of free-radical reactions, namely Fe2+. Most likely, iron chelators will need to be included in lung pathology treatment, particularly in children to prevent an intensification of OS, underlying the development of multiple organ deficiency.
1. Suki B, Lutchen R, Ingenito ER. On the progressive nature of emphysema. Role of proteases, inflammation and mechanical force. Am J respire Crit Care Med 2003; 168:516-521.
2. Lucatteli M, Baralesi B, Cavarra E, et al. Is neutrophil elastase the missing link between emphysema and fibrosis. Evidence from two mouse models. Resp Research 2005; 6:83.
3. Parks WC, Shapiro SD. Matrix metalloproteinases in lung biology. Respir Res 2001; 2:10-19.
4. Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. European Respiratory J 2003; 22(4):672-688.
5. Zheng T, Zhu Z, Wang Z, et al. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase – and cathepsin-dependent emphysema. J Clin Invest 2000; 106:1081-1093.
6. Emel’yanov AV, Shevelev CE, Dolgodvorov AF. Macro and microelenemtary turnover .Inflammation mechanism in bronchus and antiinflamation therapy. SpB, Nirmedizdat 1998.
7. Rakitsky VN, Yudina TV. Antioxidant and microelement status of the organism: present-day diagnostic problems. Bulletin of the Russian Academy of Medical Sciences 2005;3:33-36.
8. Wisotsky AG. Bullous emphysema: etiology, pathogenesis; classification. Donetsk, 2007.
9. Schnebli HP, Christen P, Jochum M, et al. Plasma Levels of Inhibitor-Bound Leukocytic Elastase in Rheumatoid Arthrits Patients. In: Heidland A, Horl WH, eds. Proteinases: potential role in health and disease. London: Plenum, 1984: 345-53.
10. Dunsmore SE, Saarialho-Kere UK, Roby JD, et al. Matrilysin expression and function in airway epithelium. J Clin Invest 1998; 102:1321-1331.
11.Taraseviciene-Stewart L, Voelkel NF. Molecular pathogenesis of emphysema. J Clinical Investigation 2008; 118 (2):394-402.
12. Li Q, Parc PW, Wilson CL, Parcs WC. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell 2002; 111: 635-646.
13. Zorin NA, Zorina VN, Zorina RM. The Role of Macroglobuli family proteins in regulation of inflammation reactions. Biomedical chemistry 2006; 52:229-238.
14. Reece ST, Loddenkemper Ch, Askew DJ, et al. Serine protease activity contributes to control of Mycobacterium tuberculosis in hypoxic lung granulomas in mice. J Clin Invest 2010; 120 (9):3365-3376.
15. Foronjy R, DArmiento J.The role of collagenase in emphysema. Respir Res 2001; 2:348-352.
16. Morris DG, Huang X, Kaminski N, et al. Loss of integrin-mediated TGF-beta activation causes MMP-12 dependent pulmonary emphysema. Nature 2003; 422:169-173.
17. Orlov YuP, Dolgich VT. Iron metabolism in biological systems (biochemical, pathophysiological and clinical perspectives). Biomedical chemistry 2007; 53 (1):25-38.
The fully formatted PDF version is available.
Int J Biomed. 2012;2(3):222-227.© 2012 International Medical Research and Development Corporation. All rights reserved.