Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis.
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.
Department of Pharmacology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, Canada J1H 5N4.
Louisane
0000-0001-7861-9813
L
Desbiens
Department of Pharmacology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, Canada J1H 5N4.
Catherine
0000-0002-0636-7781
C
Lapointe
Department of Pediatrics, Program of Immunology and Allergology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, Canada J1H 5N4.
Marjan
M
Gharagozloo
Department of Pediatrics, Program of Immunology and Allergology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, Canada J1H 5N4.
Shaimaa
S
Mahmoud
Department of Medical Biochemistry and Microbiology, Uppsala University BMC, Box 582, 75123 Uppsala, Sweden; Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, P.O. Box 7070, 75007 Uppsala, Sweden.
Gunnar
0000-0002-6779-391X
G
Pejler
Department of Pediatrics, Program of Immunology and Allergology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, Canada J1H 5N4.
Denis
D
Gris
Department of Pharmacology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, Canada J1H 5N4.
Pedro
0000-0002-9863-3548
P
D'Orléans-Juste
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D019332:Endothelin-1; D012697:Serine Endopeptidases; C066932:mast cell protease 4