Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2016 Sep 10

PMID 27610007

Citations 8

Authors

Louisane Desbiens

Catherine Lapointe

Marjan Gharagozloo

Shaimaa Mahmoud

Gunnar Pejler

Denis Gris

Pedro DOrleans-Juste

Affiliations

Soon will be listed here.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized with MOG35-55 plus complete Freund's adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO congeners. Together, the present study supports a role for mMCP-4 in the early inflammatory phases of the disease in a mouse model of MS.

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References

Heuston S, Hyland N . Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders?. Br J Pharmacol. 2012; 167(4):732-40. PMC: 3575774. DOI: 10.1111/j.1476-5381.2012.02055.x. View

Semaan W, Desbiens L, Houde M, Labonte J, Gagnon H, Yamamoto D . Chymase inhibitor-sensitive synthesis of endothelin-1 (1-31) by recombinant mouse mast cell protease 4 and human chymase. Biochem Pharmacol. 2015; 94(2):91-100. DOI: 10.1016/j.bcp.2015.02.001. View

Tchougounova E, Pejler G, Abrink M . The chymase, mouse mast cell protease 4, constitutes the major chymotrypsin-like activity in peritoneum and ear tissue. A role for mouse mast cell protease 4 in thrombin regulation and fibronectin turnover. J Exp Med. 2003; 198(3):423-31. PMC: 2194091. DOI: 10.1084/jem.20030671. View

Walker M, Hatfield J, Brown M . New insights into the role of mast cells in autoimmunity: evidence for a common mechanism of action?. Biochim Biophys Acta. 2011; 1822(1):57-65. PMC: 4424662. DOI: 10.1016/j.bbadis.2011.02.009. View

Gregory G, Robbie-Ryan M, Secor V, Sabatino Jr J, Brown M . Mast cells are required for optimal autoreactive T cell responses in a murine model of multiple sclerosis. Eur J Immunol. 2005; 35(12):3478-86. DOI: 10.1002/eji.200535271. View

Russi A, Walker-Caulfield M, Brown M . Mast cell inflammasome activity in the meninges regulates EAE disease severity. Clin Immunol. 2016; 189:14-22. DOI: 10.1016/j.clim.2016.04.009. View

Jankowska-Lech I, Terelak-Borys B, Grabska-Liberek I, Palasik W, Bik W, Wolinska-Witort E . Decreased endothelin-1 plasma levels in multiple sclerosis patients: a possible factor of vascular dysregulation?. Med Sci Monit. 2015; 21:1066-71. PMC: 4403550. DOI: 10.12659/MSM.890899. View

Wu Q, Kuo H, Deng G . Serine proteases and cardiac function. Biochim Biophys Acta. 2005; 1751(1):82-94. DOI: 10.1016/j.bbapap.2004.09.005. View

Kerschensteiner M, Bareyre F, Buddeberg B, Merkler D, Stadelmann C, Bruck W . Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis. J Exp Med. 2004; 200(8):1027-38. PMC: 2211840. DOI: 10.1084/jem.20040452. View

10.

Pache M, Kaiser H, Akhalbedashvili N, Lienert C, Dubler B, Kappos L . Extraocular blood flow and endothelin-1 plasma levels in patients with multiple sclerosis. Eur Neurol. 2003; 49(3):164-8. DOI: 10.1159/000069085. View

11.

Andersson M, Karlson U, Hellman L . The extended cleavage specificity of the rodent beta-chymases rMCP-1 and mMCP-4 reveal major functional similarities to the human mast cell chymase. Mol Immunol. 2007; 45(3):766-75. DOI: 10.1016/j.molimm.2007.06.360. View

12.

Costanza M, Colombo M, Pedotti R . Mast cells in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. Int J Mol Sci. 2012; 13(11):15107-25. PMC: 3509630. DOI: 10.3390/ijms131115107. View

13.

Palaniyandi S, Nagai Y, Watanabe K, Ma M, Veeraveedu P, Prakash P . Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. Exp Biol Med (Maywood). 2007; 232(9):1213-21. DOI: 10.3181/0703-RM-85. View

14.

Haufschild T, Shaw S, Kesselring J, Flammer J . Increased endothelin-1 plasma levels in patients with multiple sclerosis. J Neuroophthalmol. 2001; 21(1):37-8. DOI: 10.1097/00041327-200103000-00011. View

15.

Ohsawa K, Imai Y, Sasaki Y, Kohsaka S . Microglia/macrophage-specific protein Iba1 binds to fimbrin and enhances its actin-bundling activity. J Neurochem. 2004; 88(4):844-56. DOI: 10.1046/j.1471-4159.2003.02213.x. View

16.

Reber L, Daubeuf F, Pejler G, Abrink M, Frossard N . Mast cells contribute to bleomycin-induced lung inflammation and injury in mice through a chymase/mast cell protease 4-dependent mechanism. J Immunol. 2014; 192(4):1847-54. DOI: 10.4049/jimmunol.1300875. View

17.

Frenzel L, Hermine O . Mast cells and inflammation. Joint Bone Spine. 2012; 80(2):141-5. DOI: 10.1016/j.jbspin.2012.08.013. View

18.

Gharagozloo M, Mahvelati T, Imbeault E, Gris P, Zerif E, Bobbala D . The nod-like receptor, Nlrp12, plays an anti-inflammatory role in experimental autoimmune encephalomyelitis. J Neuroinflammation. 2015; 12:198. PMC: 4628289. DOI: 10.1186/s12974-015-0414-5. View

19.

DHaeseleer M, Beelen R, Fierens Y, Cambron M, Vanbinst A, Verborgh C . Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1. Proc Natl Acad Sci U S A. 2013; 110(14):5654-8. PMC: 3619305. DOI: 10.1073/pnas.1222560110. View

20.

Brahmachari S, Fung Y, Pahan K . Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide. J Neurosci. 2006; 26(18):4930-9. PMC: 1963412. DOI: 10.1523/JNEUROSCI.5480-05.2006. View