Immunology; Immunology and Allergy; Asthma; ADAM; ADAM28; metalloproteinases; mouse models
Abstract :
[en] BackgroundAsthma is characterized by morphological modifications of the airways (inflammation and remodelling) and bronchial hyperresponsiveness. Mechanisms linking these two key features of asthma are still poorly understood. ADAM28 (a disintegrin and metalloproteinase 28) might play a role in asthma pathophysiology. ADAM28 exists as membrane-bound and soluble forms and is mainly expressed by lymphocytes and epithelial cells.MethodsADAM28-/- mice and ADAM28+/+ counterparts were sensitized and exposed to ovalbumin (OVA). Airway responsiveness was measured using the flexiVent® system. After sacrifice, bronchoalveolar lavage (BAL) was performed and lungs were collected for analysis of airway inflammation and remodelling.ResultsThe expression of the soluble form of ADAM28 was lower in the lungs of OVA-exposed mice (as compared to PBS-exposed mice) and progressively increased in correlation with the duration of allergen exposure. In lungs of ADAM28-/- mice exposed to allergens, the proportion of Th2 cells among <jats:inline-formula><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="im1"><mml:mrow><mml:msubsup><mml:mrow><mml:mtext>CD</mml:mtext></mml:mrow><mml:mn>4</mml:mn><mml:mo>+</mml:mo></mml:msubsup></mml:mrow></mml:math></jats:inline-formula> cells and the number of B cells were decreased. Bronchial responsiveness was lower in ADAM28-/- mice exposed to allergens and similar to the responsiveness of sham-challenged mice. Similarly, features of airway remodelling (collagen deposition, smooth muscle hyperplasia, mucous hyperplasia) were significantly less developed in OVA-exposed ADAM28-/- animals in sharp contrasts to ADAM28+/+. In addition, we report the first evidence of ADAM28 RNA expression by lung fibroblasts and we unveil a decreased capacity of lung fibroblasts extracted from OVA-exposed ADAM28-/- mice to proliferate as compared to those extracted from OVA-exposed ADAM28+/+ suggesting a direct contribution of this enzyme to the modulation of airway remodelling.ConclusionThese results suggest that ADAM28 might be a key contributor to the pathophysiology of asthma.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bendavid, Guillaume
Hubeau, Céline
Perin, Fabienne ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Global Initiative for Asthma. Global strategy for asthma management and prevention 2021. Available at: www.ginasthma.org.
Lange P Parner J Vestbo J Schnohr P Jensen G. A 15-year follow-up study of ventilatory function in adults with asthma. N Engl J Med (1998) 339(17):1194–200. doi: 10.1056/NEJM199810223391703
Smith BM Zhao N Olivenstein R Lemiere C Hamid Q Martin JG. Asthma and fixed airflow obstruction: Long-term trajectories suggest distinct endotypes. Clin Exp Allergy (2021) 51(1):39–48. doi: 10.1111/cea.13714
Boulet LP. Airway remodelling in asthma: update on mechanisms and therapeutic approaches. Curr Opin Pulm Med (2018) 24(1):56–62. doi: 10.1097/MCP.0000000000000441
Holgate ST. The airway epithelium is central to the pathogenesis of asthma. Allergol Int (2008) 57(1):1–10. doi: 10.2332/allergolint.R-07-154
Bayram H Devalia JL Khair OA Abdelaziz MM Sapsford RJ Sagai M et al. Comparison of ciliary activity and inflammatory mediator release from bronchial epithelial cells of nonatopic nonasthmatic subjects and atopic asthmatic patients and the effect of diesel exhaust particles in vitro. J Allergy Clin Immunol (1998) 102(5):771–82. doi: 10.1016/S0091-6749(98)70017-X
Reeves SR Barrow KA Kolstad TK White MP Rich LM Wight TN et al. Fibroblast gene expression following asthmatic bronchial epithelial cell conditioning correlates with epithelial donor lung function and exacerbation history. Sci Rep (2018) 8(1):15768. doi: 10.1038/s41598-018-34021-6
Reeves SR Kolstad T Lien T-Y Elliott M Ziegler SF Wight TN et al. Asthmatic airway epithelial cells differentially regulate fibroblast expression of extracellular matrix components. J Allergy Clin Immunol (2014) 134(3):663–70 e1. doi: 10.1016/j.jaci.2014.04.007
Liu G Philp AM Corte T Travis MA Schilter H Hansbro NG et al. Therapeutic targets in lung tissue remodelling and fibrosis. Pharmacol Ther (2021) 225:107839. doi: 10.1016/j.pharmthera.2021.107839
Ong CH Tham CL Harith HH Firdaus N Israf DA. TGF-β-induced fibrosis: A review on the underlying mechanism and potential therapeutic strategies. Eur J Pharmacol (2021) 911:174510. doi: 10.1016/j.ejphar.2021.174510
Rocks N Paulissen G G El Hour M Quesada F Crahay C Gueders M et al. Emerging roles of ADAM and ADAMTS metalloproteinases in cancer. Biochimie (2008) 90:369–79. doi: 10.1016/j.biochi.2007.08.008
Dreymueller D Uhlig S Ludwig A. ADAM-family metalloproteinases in lung inflammation: potential therapeutic targets. J Physiol Lung Cell Mol Physiol (2015) 308(4):325–43. doi: 10.1152/ajplung.00294.2014
Paulissen G Rocks N Gueders MM Crahay C Quesada-Calvo F Bekaert S et al. Role of ADAM and ADAMTS metalloproteinases in airway diseases. Respir Res (2009) 10:127. doi: 10.1186/1465-9921-10-127
Paulissen G El Hour M Rocks N Guéders MM Bureau F Foidart JM et al. Control of allergen-induced inflammation and hyperresponsiveness by the metalloproteinase ADAMTS-12. J Immunol (2012) 189(8):4135–43. doi: 10.4049/jimmunol.1103739
Mochizuki S Shimoda M Shiomi T Fujii Y Okada Y. ADAM28 is activated by MMP-7 matrilysin-1) and cleaves insulin-like growth factor binding protein-3. Biochem Biophys Res Commun (2004) 315:79–84. doi: 10.1016/j.bbrc.2004.01.022
Lee JY Park SW Chang HK Kim HY Rhim T Lee JH et al. A disintegrin and metalloproteinase 33 protein in patients with asthma relevance to airflow limitation. AJRCCM (2006) 173(7):729–35. doi: 10.1164/rccm.200409-1175OC
McGinn OJ English WR Roberts S Ager A Newham P Murphy G. Modulation of integrin α4β1 by ADAM28 promotes lymphocyte adhesion and transendothelial migration. Cell Biol Int (2011) 35(10):1043–53. doi: 10.1042/CBI20100885
Di Valentin E Crahay C Garbacki N Hennuy B Guéders M Noël A et al. New asthma biomarkers: lessons from murine models of acute and chronic asthma. AJP-Lung Cell Mol Physiol (2009) 296:2:L185–97. doi: 10.1152/ajplung.90367.2008
Miyamae Y Mochizuki S Shimoda M Ohara K Abe H Yamashita S et al. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death. FEBS J (2016) 283(9):1574–94. doi: 10.1111/febs.13693
Gérard C Hubeau C Carnet O Bellefroid M Sounni N Blacher S et al. Microenvironment-derived ADAM28 prevents cancer dissemination. Oncotarget (2018) 9:37185–99. doi: 10.18632/oncotarget.26449
Gueders MM Bertholet P Perin F Rocks N Maree R Botta V et al. A novel formulation of inhaled doxycycline reduces allergen-induced inflammation, hyperresponsiveness and remodeling by matrix metalloproteinases and cytokines modulation in a mouse model of asthma. Biochem Pharmacol (2008) 75:514–26. doi: 10.1016/j.bcp.2007.09.012
Seluanov A Vaidya A Gorbunova V. Establishing primary adult fibroblast cultures from rodents. J Vis Exp (2010) 44):2033. doi: 10.3791/2033
Bekhouche M Leduc C Dupont L Janssen L Delolme F Vadon-Le Goff S et al. Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-β signaling as primary targets. FASEB J (2016) 30(5):1741–56. doi: 10.1096/fj.15-279869
Fourie AM Coles F Moreno V Karlsson L. Catalytic activity of ADAM8, ADAM15, and MDC-l (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23J. Biol Chem (2003) 278:30469. doi: 10.1074/jbc.M213157200
Acharya M Borland G Edkins AL Maclellan LM Matheson J Ozanne BW et al. CD23/FcϵRII: molecular multi-tasking. Clin Exp Immunol (2010) 162(1):12–23. doi: 10.1111/j.1365-2249.2010.04210.x
Paulissen G Rocks N Guéders MM Bedoret D Crahay C Quesada-Calvo F et al. ADAM-8, a metalloproteinase, drives acute allergen-induced airway inflammation. Eur J Immunol (2011) 41:380–91. doi: 10.1002/eji.200940286
Matsuno O Kumamoto T Higuchi Y. ADAM8 in allergy. Inflammation Allergy Drug Targets. (2008) 7(2):108–12. doi: 10.2174/187152808785107598
Weskamp G Ford JW Sturgill J Martin S Docherty AJ Swendeman S et al. ADAM10 is a principal ‘sheddase’ of the low-affinity immunoglobulin e receptor CD23. Nat Immunol (2006) 7(12):1293–8. doi: 10.1038/ni1399
Villazala-Merino S Rodriguez-Dominguez A Stanek V Campion NJ Gattinger P Hofer G et al. Allergen-specific IgE levels and the ability of IgE-allergen complexes to cross-link determine the extent of CD23-mediated T-cell activation. J Allergy Clin Immunol (2020) 145(3):958–967.e5. doi: 10.1016/j.jaci.2019.11.019
Poole JA Meng J Reff M Spellman MC Rosenwasser LJ. Anti-CD23 monoclonal antibody, lumiliximab, inhibited allergen-induced responses in antigen-presenting cells and T cells from atopic subjects. J Allergy Clin Immunol (2005) 116(4):780–8. doi: 10.1016/j.jaci.2005.07.007
Saldanha-Gama RF Moraes JA Mariano-Oliveira A Coelho AL Walsh EM Marcinkiewicz C et al. alpha(9)beta(1) integrin engagement inhibits neutrophil spontaneous apoptosis: involvement of bcl-2 family members. Biochim Biophys Acta (2010) 1803(7):848–57. doi: 10.1016/j.bbamcr.2010.03.012
Roberts CM Tani PH Bridges LC Laszik Z Bowditch RD. MDC-l, a novel metalloprotease disintegrin cysteine-rich protein family member expressed by human lymphocytes. J Biol Chem (1999) 274(41):29251–9. doi: 10.1074/jbc.274.41.29251
Bridges LC Sheppard D Bowditch RD. ADAM disintegrin-like domain recognition by the lymphocyte integrins alpha4beta1 and alpha4beta7. Biochem J (2005) 387(Pt 1):101–8. doi: 10.1042/BJ20041444
Bridges LC Tani PH Hanson KR Roberts CM Judkins MB Bowditch RD. The lymphocyte metalloprotease MDC-l (ADAM 28) is a ligand for the integrin alpha4beta1. J Biol Chem (2002) 277(5):3784–92. doi: 10.1074/jbc.M109538200
Haidl ID Huber G Eichmann K. An ADAM family member with expression in thymic epithelial cells and related tissues. Gene (2002) 283(1-2):163–70. doi: 10.1016/S0378-1119(01)00871-X
Lourenço O Fonseca AM Taborda-Barata L. Human CD8+ T cells in asthma: Possible pathways and roles for NK-like subtypes. Front Immunol (2016) 7:638. doi: 10.1016/j.bbamcr.2010.03.012
Doherty TA Soroosh P Broide DH Croft M. CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling. Am J Physiol Lung Cell Mol Physiol (2009) 296(2):L229–35. doi: 10.1152/ajplung.90543.2008
Dakhama A Collins ML Ohnishi H Goleva E Leung DY Alam R et al. IL-13-producing BLT1-positive CD8 cells are increased in asthma and are associated with airway obstruction. Allergy (2013) 68(5):666–73. doi: 10.1111/all.12135
Borowski A Kuepper M Horn U Knüpfer U Zissel G Höhne K et al. Interleukin-13 acts as an apoptotic effector on lung epithelial cells and induces pro-fibrotic gene expression in lung fibroblasts. Clin Exp Allergy (2008) 38(4):619–28. doi: 10.1111/j.1365-2222.2008.02944.x
Jowett JB Okada Y Leedman PJ Curran JE Johnson MP Moses EK et al. ADAM28 is elevated in humans with the metabolic syndrome and is a novel sheddase of human tumour necrosis factor-α. Immunol Cell Biol (2012) 90(10):966–73. doi: 10.1038/icb.2012.44
Wu Z Zhou J Xiao Y Ming J Zhou J Dong F et al. CD20+CD22+ADAM28+ b cells in tertiary lymphoid structures promote immunotherapy response. Front Immunol (2022) 13:865596. doi: 10.3389/fimmu.2022.865596