MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters

Respiratory Research

Michael D Weiden⁴  William N Rom³  David J Prezant¹  Ashley L Comfort²  Bushra Naveed⁵  Soo Jung Cho²  Sophia Kwon²  Anna Nolan⁵ 

[1] Department of Medicine, Pulmonary Medicine Division, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx NY, USA;Division of Pulmonary, Critical Care and Sleep, New York University, School of Medicine, 462 First Avenue, NB7N24, New York NY, USA;Department of Environmental Medicine, New York University, School of Medicine, 57 Old Forge Road, Tuxedo Park NY, USA;Department of Medicine and Environmental Medicine, 550 1st Avenue, New York, NY 10016, USA;Fire Department of New York, Bureau of Health Services and Office of Medical Affairs, Brooklyn NY, USA

关键词: Occupational exposure;    Lung disease;    Biomarkers;   

Others  :  790795
DOI  :  10.1186/1465-9921-15-5

 received in 2013-04-12, accepted in 2013-12-10,  发布年份 2014

【 摘 要 】

Rationale

After 9/11/2001, most FDNY workers had persistent lung function decline but some exposed workers recovered. We hypothesized that the protease/anti-protease balance in serum soon after exposure predicts subsequent recovery.

Methods

We performed a nested case–control study measuring biomarkers in serum drawn before 3/2002 and subsequent forced expiratory volume at one second (FEV₁) on repeat spirometry before 3/2008. Serum was assayed for matrix metalloproteinases (MMP-1,2,3,7,8,9,12 and 13) and tissue inhibitors of metalloproteinases (TIMP-1,2,3,4). The representative sub-cohort defined analyte distribution and a concentration above 75^th percentile defined elevated biomarker expression. An FEV₁ one standard deviation above the mean defined resistance to airway injury. Logistic regression was adjusted for pre-9/11 FEV₁, BMI, age and exposure intensity modeled the association between elevated biomarker expression and above average FEV₁.

Results

FEV₁ in cases and controls declined 10% of after 9/11/2001. Cases subsequently returned to 99% of their pre-exposure FEV₁ while decline persisted in controls. Elevated TIMP-1 and MMP-2 increased the odds of resistance by 5.4 and 4.2 fold while elevated MMP-1 decreased it by 0.27 fold.

Conclusions

Resistant cases displayed healing, returning to 99% of pre-exposure values. High TIMP-1 and MMP-2 predict healing. MMP/TIMP balance reflects independent pathways to airway injury and repair after WTC exposure.

【 授权许可】

   
2014 Nolan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 2.

Figure 3.

【 参考文献 】

• [1]Landrigan PJ: Health consequences of the 11 September 2001 attacks. Environ Health Perspect 2001, 109(11):A514-A515. Epub 2001/11/20
• [2]Claudio L: Environmental aftermath. Environ Health Perspect 2001, 109(11):A528-A536. Epub 2001/11/20
• [3]Aldrich TK, Gustave J, Hall CB, Cohen HW, Webber MP, Zeig-Owens R, et al.: Lung function in rescue workers at the World Trade Center after 7 years. N Engl J Med 2010, 362(14):1263-72. Epub 2010/04/09
• [4]Weiden MD, Naveed B, Kwon S, Segal LN, Cho SJ, Tsukiji J, et al.: Comparison of WTC dust size on macrophage inflammatory cytokine release in vivo and in vitro. PLoS One 2012, 7(7):e40016. Epub 2012/07/21
• [5]Naveed B, Weiden MD, Kwon S, Gracely EJ, Comfort AL, Ferrier N, et al.: Metabolic syndrome biomarkers predict lung function impairment: a nested case–control study. Am J Respir Crit Care Med 2012, 185(4):392-399. Epub 2011/11/19
• [6]Nolan A, Naveed B, Comfort AL, Ferrier N, Hall CB, Kwon S, et al.: Inflammatory biomarkers predict airflow obstruction after exposure to World Trade Center dust. Chest 2011, 142(2):412-8. Epub 2011/10/15
• [7]Hunninghake GM, Cho MH, Tesfaigzi Y, Soto-Quiros ME, Avila L, Lasky-Su J, et al.: MMP12, lung function, and COPD in high-risk populations. N Engl J Hum Serv 2009, 361(27):2599-2608. Epub 2009/12/19
• [8]Rosas IO, Richards TJ, Konishi K, Zhang Y, Gibson K, Lokshin AE, et al.: MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Med 2008, 5(4):e93. Epub 2008/05/02
• [9]Jones CB, Sane DC, Herrington DM: Matrix metalloproteinases: a review of their structure and role in acute coronary syndrome. Cardiovasc Res 2003, 59(4):812-823. Epub 2003/10/14
• [10]Death AK, Nakhla S, McGrath KC, Martell S, Yue DK, Jessup W, et al.: Nitroglycerin upregulates matrix metalloproteinase expression by human macrophages. J Am Coll Cardiol 2002, 39(12):1943-1950. Epub 2002/06/27
• [11]Imai K, Dalal SS, Chen ES, Downey R, Schulman LL, Ginsburg M, et al.: Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema. Am J Respir Crit Care Med 2001, 163(3 Pt 1):786-791. Epub 2001/03/20
• [12]Geraghty P, Dabo AJ, D’Armiento J: TLR4 protein contributes to cigarette smoke-induced matrix metalloproteinase-1 (MMP-1) expression in chronic obstructive pulmonary disease. J Biol Chem 2011, 286(34):30211-30218. Epub 2011/07/07
• [13]Vandenbroucke RE, Dejonckheere E, Libert C: A therapeutic role for matrix metalloproteinase inhibitors in lung diseases? Eur Respir J 38(5):1200-1214. Epub 2011/06/11
• [14]Martin MD, Matrisian LM: The other side of MMPs: protective roles in tumor progression. Cancer Metastasis Rev 2007, 26(3–4):717-724. Epub 2007/08/25
• [15]Elkington PT, Friedland JS: Matrix metalloproteinases in destructive pulmonary pathology. Thorax 2006, 61(3):259-266. Epub 2005/10/18
• [16]Joos L, He JQ, Shepherdson MB, Connett JE, Anthonisen NR, Pare PD, et al.: The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function. Hum Mol Genet 2002, 11(5):569-576. Epub 2002/03/05
• [17]Gosselink JV, Hayashi S, Elliott WM, Xing L, Chan B, Yang L, et al.: Differential expression of tissue repair genes in the pathogenesis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010, 181(12):1329-1335. Epub 2010/01/16
• [18]Maclay JD, McAllister DA, Rabinovich R, Haq I, Maxwell S, Hartland S, et al.: Systemic elastin degradation in chronic obstructive pulmonary disease. Thorax 2012, 67(7):606-612. Epub 2012/03/01
• [19]Weiden MD, Ferrier N, Nolan A, Rom WN, Comfort A, Gustave J, et al.: Obstructive airways disease with air trapping among firefighters exposed to World Trade Center dust. Chest 2010, 137(3):566-574. Epub 2009/10/13
• [20]Weiden MD, Naveed B, Kwon S, Cho SJ, Comfort AL, Prezant DJ, et al.: Cardiovascular biomarkers predict susceptibility to lung injury in World Trade Center dust-exposed firefighters. Eur Respir J 2013, 41(5):1023-30. Epub 2012/08/21
• [21]Rundle AG, Vineis P, Ahsan H: Design options for molecular epidemiology research within cohort studies. Cancer Epidemiol Biomarkers Prev 2005, 14(8):1899-1907. Epub 2005/08/17
• [22]Shaker SB, von Wachenfeldt KA, Larsson S, Mile I, Persdotter S, Dahlback M, et al.: Identification of patients with chronic obstructive pulmonary disease (COPD) by measurement of plasma biomarkers. Clin Respir J 2008, 2(1):17-25. Epub 2008/01/01
• [23]Ziora D, Dworniczak S, Kozielski J: Induced sputum metalloproteinases and their inhibitors in relation to exhaled nitrogen oxide and sputum nitric oxides and other inflammatory cytokines in patients with chronic obstructive pulmonary disease. J Physiol Pharmacol 2008, 59(Suppl 6):809-817. Epub 2009/02/28
• [24]Engstrom G, Lindberg C, Gerhardssonde Verdier M, Nihlen U, Anderson M, Svartengren M, et al.: Blood biomarkers and measures of pulmonary function--a study from the Swedish twin registry. Respir Med 2012, 106(9):1250-1257. Epub 2012/06/13
• [25]Ambalavanan N, Nicola T, Li P, Bulger A, Murphy-Ullrich J, Oparil S, et al.: Role of matrix metalloproteinase-2 in newborn mouse lungs under hypoxic conditions. Pediatr Res 2008, 63(1):26-32. Epub 2007/11/29
• [26]Tchougounova E, Lundequist A, Fajardo I, Winberg JO, Abrink M, Pejler G: A key role for mast cell chymase in the activation of pro-matrix metalloprotease-9 and pro-matrix metalloprotease-2. J Biol Chem 2005, 280(10):9291-9296. Epub 2004/12/24
• [27]Kheradmand F, Kiss A, Xu J, Lee SH, Kolattukudy PE, Corry DB: A protease-activated pathway underlying Th cell type 2 activation and allergic lung disease. J Immunol 2002, 169(10):5904-5911. Epub 2002/11/08
• [28]Caplan-Shaw CE, Yee H, Rogers L, Abraham JL, Parsia SS, Naidich DP, et al.: Lung pathologic findings in a local residential and working community exposed to World Trade Center dust, gas, and fumes. J Occup Environ Med 2011, 53(9):981-991. Epub 2011/08/24
• [29]Corry DB, Rishi K, Kanellis J, Kiss A, Song Lz LZ, Xu J, et al.: Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency. Nat Immunol 2002, 3(4):347-353. Epub 2002/03/12
• [30]Gonzalez-Lopez A, Astudillo A, Garcia-Prieto E, Fernandez-Garcia MS, Lopez-Vazquez A, Batalla-Solis E, et al.: Inflammation and matrix remodeling during repair of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 2011, 301(4):L500-L509. Epub 2011/07/12
• [31]D’Armiento J, Dalal SS, Okada Y, Berg RA, Chada K: Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 1992, 71(6):955-961. Epub 1992/12/11