Suppression of cell-transferred experimental autoimmune encephalomyelitis in defibrinated Lewis rats

Inoue, Akira; Koh, Chang−Sung; Shimada, Kinji; Yanagisawa, Nobuo; Yoshimura, Kazuhiko

doi:10.1016/s0165-5728(96)00150-6

Cited by 38 publications

(36 citation statements)

References 26 publications

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“…Fibrin can directly stimulate expression of IL-1b and TNF-a in mononuclear cells and can induce production of the chemokines CXCL8 and CCL2 by endothelial cells and fibroblasts, promoting the migration of leukocytes and macrophages (8,24). Indeed, some evidence suggests that removal of fibrin can diminish disease development and symptoms (8,(25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression

Takabayashi

Kato²,

Peters³

et al. 2013

Am J Respir Crit Care Med

141

205

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Rationale: Nasal polyps (NPs) are characterized by intense edema or formation of pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms underlying NP retention of plasma proteins in their submucosa remain unclear. Objectives: We hypothesized that formation of a fibrin mesh retains plasma proteins in NPs. We assessed the fibrin deposition and expression of the components of the fibrinolytic system in patients with chronic rhinosinusitis (CRS). Methods:We assessed fibrin deposition in nasal tissue from patients with CRS and control subjects by means of immunofluorescence. Fibrinolytic components, d-dimer, and plasminogen activators were measured using ELISA, real-time PCR, and immunohistochemistry. We also performed gene expression and protein quantification analysis in cultured airway epithelial cells. Measurements and Main Results: Immunofluorescence data showed profound fibrin deposition in NP compared with uncinate tissue (UT) from patients with CRS and control subjects. Levels of the cross-linked fibrin cleavage product protein, d-dimer, were significantly decreased in NP compared with UT from patients with CRS and control subjects, suggesting reduced fibrinolysis (P , 0.05). Expression levels of tissue plasminogen activator (t-PA) mRNA and protein were significantly decreased in NP compared with UT from patients with CRS and control subjects (P , 0.01). Immunohistochemistry demonstrated clear reduction of t-PA in NP, primarily in the epithelium and glands. Th2 cytokine-stimulated cultured airway epithelial cells showed down-regulation of t-PA, suggesting a potential Th2 mechanism in NP. Conclusions: A Th2-mediated reduction of t-PA might lead to excessive fibrin deposition in the submucosa of NP, which might contribute to the tissue remodeling and pathogenesis of CRS with nasal polyps.

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Section: Discussionmentioning

confidence: 99%

Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression

Takabayashi

Kato²,

Peters³

et al. 2013

Am J Respir Crit Care Med

141

205

View full text Add to dashboard Cite

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“…Perivascular fibrinogen͞fibrin deposits are found in EAE and inflammatory MS lesions (37,38). Interestingly, dermatan sulfate and batroxobin, which degrade fibrinogen and suppress fibrin deposition, respectively, were shown to ameliorate EAE (39,40).…”

Section: H1r (C) Is Not Detected Although Rare Astrocytes and Choroimentioning

confidence: 99%

Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination

Pedotti

DeVoss

Youssef

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

117

118

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“…The ensuing coagulation cascade culminates with the generation of thrombin, a protease that cleaves extravasated fibrinogen, prompting its polymerization and deposition as fibrin. Accordingly, localized extravascular fibrin deposition accompanies many type 1 T helper cell (Th1)-associated responses, including autoimmune neuropathologies, [1][2][3][4] glomerulonephritis, 5,6 rheumatoid arthritis, [7][8][9] Crohn's disease, 10,11 allograft rejection, 12,13 delayed-type hypersensitivity, [14][15][16][17][18][19] and viral infections. 20,21 For some time, it has been appreciated that such Th1-associated coagulation has physiologic consequences, as the swelling that accompanies delayed-type hypersensitivity responses is suppressed in anticoagulated or fibrinogen-deficient subjects.…”

Section: Introductionmentioning

confidence: 99%

Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo

Szaba

Smiley

2002

Blood

281

224

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Extravascular coagulation leading to fibrin deposition accompanies many immune and inflammatory responses. Although recognized by pathologists for decades, and probably pathologic under certain conditions, the physiologic functions of extravascular coagulation remain to be fully defined. This study demonstrates that thrombin can activate macrophage adhesion and prompt interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production in vivo. Peritoneal macrophages were elicited with thioglycollate (TG) and then activated in situ, either by intraperitoneal injection of lipopolysaccharide (LPS) or by injection of antigen into mice bearing antigen-primed T cells. Others previously established that such treatments stimulate macrophage adhesion to the mesothelial lining of the peritoneal cavity. The present study demonstrates that thrombin functions in this process, as macrophage adhesion was suppressed by Refludan, a highly specific thrombin antagonist, and induced by direct peritoneal administration of purified thrombin. Although recent studies established that protease activated receptor 1 (PAR-1) mediates some of thrombin's proinflammatory activities macrophage adhesion occurred normally in PAR-1-deficient mice. However, adhesion was suppressed in fibrin(ogen)-deficient mice, suggesting that fibrin formation stimulates macrophage adhesion in vivo. This study also suggests that fibrin regulates chemokine/cytokine production in vivo, as direct injection of thrombin stimulated peritoneal accumulation of IL-6 and MCP-1 in a fibrin(ogen)-dependent manner. Given that prior studies have clearly established inflammatory roles for PAR-1, thrombin probably has pleiotropic functions during inflammation, stimulating vasodilation and mast cell degranulation via PAR-1, and activating cytokine/chemokine production and macrophage adhesion via fibrin(ogen). IntroductionVasodilation and increased vascular permeability are among the earliest signs of inflammation. These events stimulate the extravasation of inactive coagulant precursors, which become activated upon exposure to extravascular tissues. The ensuing coagulation cascade culminates with the generation of thrombin, a protease that cleaves extravasated fibrinogen, prompting its polymerization and deposition as fibrin. Accordingly, localized extravascular fibrin deposition accompanies many type 1 T helper cell (Th1)-associated responses, including autoimmune neuropathologies, 1-4 glomerulonephritis, 5,6 rheumatoid arthritis, 7-9 Crohn's disease, 10,11 allograft rejection, 12,13 delayed-type hypersensitivity, 14-19 and viral infections. 20,21 For some time, it has been appreciated that such Th1-associated coagulation has physiologic consequences, as the swelling that accompanies delayed-type hypersensitivity responses is suppressed in anticoagulated or fibrinogen-deficient subjects. [14][15][16][17][18][19] However, the full significance of immune-associated extravascular coagulation remains to be defined.Recent studies suggest that thrombin is a physiologic m...

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Suppression of cell-transferred experimental autoimmune encephalomyelitis in defibrinated Lewis rats

Cited by 38 publications

References 26 publications

Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression

Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression

Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination

Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo

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