The modification of experimental allergic encephalomyelitis with epsilon aminocaproic acid

Sibley, W. A.; Kiernat, James F; Laguna, Jose F.

doi:10.1212/wnl.28.9_part_2.102

Cited by 19 publications

(5 citation statements)

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“…In line with these results, treatment with a PA inhibitor-derived peptide (PAI-1-dp) that increases plasminogen activation ability of uPA, suppressed the development of EAE symptoms (see also Table 2 ) ( 38 ). In contrast, another publication using ε-aminocaproic acid, an inhibitor of plasminogen and trypsinogen activator, reported a suppression of EAE severity (see also Table 2 ) ( 65 ).…”

Section: Resultsmentioning

confidence: 97%

The Coagulation Factors Fibrinogen, Thrombin, and Factor XII in Inflammatory Disorders—A Systematic Review

et al. 2018

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BackgroundThe interaction of coagulation factors has been shown to go beyond their traditional roles in hemostasis and to affect the development of inflammatory diseases. Key molecular players, such as fibrinogen, thrombin, or factor XII have been mechanistically and epidemiologically linked to inflammatory disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), and colitis.ObjectivesTo systematically review the evidence for a role of coagulation factors, especially factor XII, fibrinogen, and thrombin in inflammatory disorders like MS, RA, and bowel disorders.MethodsA systematic literature search was done in the PubMed database to identify studies about coagulation factors in inflammatory diseases. Original articles and reviews investigating the role of the kallikrein–kinin and the coagulation system in mouse and humans were included.ResultsWe identified 43 animal studies dealing with inflammatory disorders and factors of the kallikrein–kinin or the coagulation system. Different immunological influences are described and novel molecular mechanisms linking coagulation and inflammation are reported.ConclusionA number of studies have highlighted coagulation factors to tip the balance between hemostasis and thrombosis and between protection from infection and extensive inflammation. To optimize the treatment of chronic inflammatory disorders by these factors, further studies are necessary.

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Section: Resultsmentioning

confidence: 97%

The Coagulation Factors Fibrinogen, Thrombin, and Factor XII in Inflammatory Disorders—A Systematic Review

et al. 2018

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“…Previous studies have demonstrated the ability of serine, carboxy and thiol inhibitors of proteases to suppress the development of EAE [15][16][17][18]. In this study we have used a potent hydroxamate inhibitor of gelatinase B (Ro31-9790) to assess the role of MMPs in both actively induced and adoptively transferred EAE, on the basis that it could modulate the entry of primed lymphocytes and the demyelinating potential of macrophages.…”

Section: Introductionmentioning

confidence: 99%

Suppression of experimental allergic encephalomyelitis in the Lewis rat by the matrix metalloproteinase inhibitor Ro31-9790

et al. 1995

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Matrix metalloproteinases (MMPs) are implicated in the tissue destruction associated with inflammatory demyelinating diseases such as multiple sclerosis. The effect of a hydroxamate inhibitor of MMPs, Ro31-9790, on inflammatory demyelination was assessed in two acute models of experimental allergic encephalomyelitis (EAE). Daily intraperitoneal injections of Ro31-9790 (50 mg kg-1), beginning either at the time of disease induction or from day 3 post induction, significantly reduced the clinical severity of adoptively transferred EAE. Administration of the inhibitor from the day of induction of active EAE prevented disease onset in 9/10 animals. However, in a repeat study, in which clinical disease was much more severe in the vesicle treated animals, the inhibitor was less effective. Clinical signs and CNS histopathology correlated well, with greater numbers of inflammatory lesions associated with increased disease severity. The present study confirms a role for then MMP cascade in inflammation in EAE.

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“…Elevated levels of proteolytic enzymes have been observed in and around demyelinating plaques (Einstein et al, 1972;Govindarajan et al, 1974;Rauch et al, 1973) as well as in cerebrospinal fluid in multiple sclerosis. Although such increases have been attributed to lymphocytes and macrophages Rinne and Rikkinen, 1968;Sibley et al, 1978), astrocytes also produce and secrete plasminogen activator (Toshniwal et al, 1987) suggesting that glial cells also participate in demyelination. Additionally, neutral proteinases including plasminogen activator (Brosnan et al, 1980a) degrade myelin basic protein and cause demyelination in vivo.…”

Section: Discussionmentioning

confidence: 99%

Schwann cell plasminogen activator is regulated by neurons

Clark

Zeheb²,

White

et al. 1991

Glia

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The synthesis and release of plasminogen activators (PAs) in co-cultures of embryonic rat dorsal root ganglion nerve cells (NCs) and Schwann cells (SCs) were examined by metabolic labeling, immunoprecipitation, immunodepletion, SDS-PAGE, zymography, and a two-step esterolytic assay. Metabolic labeling of SC cultures followed by immunoprecipitation of the conditioned medium (CM) demonstrated that cultured SCs synthesized and released tissue type PA (tPA). Failure of amiloride to inhibit PA activity in SCCM indicated that urokinase PA (uPA) was unlikely to contribute significantly to PA activity in SCCM. Experimental manipulation of the NCs and SCs suggested that NCs regulated SC derived PA. Total PA activity increased in SCCM 10-14-fold by 6 days after removal of NCs. Multiple molecular weight forms of PAs were detected by SDS-PAGE followed by zymography. A PA approximately 95 kDa was absent in co-cultures of SCs + NCs but prominent by 4 days postdenervation; PA approximately 50-70 kDa increased through 8 days postdenervation and PA approximately 25 kDa, present in SC + NC cultures, was absent 8 days after removal of NCs. Upon reintroduction of NCs to denervated cultures (SCs), the pattern of PAs detected in culture medium was transitional between innervated and denervated cultures. Immunodepletion experiments using conditioned medium from denervated SC cultures indicated that various molecular weight forms of PA detected in SCCM by zymography were immunologically related to tPA. These studies demonstrate that SCs synthesized and released tPA in a tissue culture model of peripheral nerve and that one mechanism for regulation of PA released by SCs was by association with NCs. This regulation occurred in cultures of both myelinating and nonmyelinating Schwann cells and thus was not dependent on the state of myelination.

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The modification of experimental allergic encephalomyelitis with epsilon aminocaproic acid

Cited by 19 publications

References 0 publications

The Coagulation Factors Fibrinogen, Thrombin, and Factor XII in Inflammatory Disorders—A Systematic Review

The Coagulation Factors Fibrinogen, Thrombin, and Factor XII in Inflammatory Disorders—A Systematic Review

Suppression of experimental allergic encephalomyelitis in the Lewis rat by the matrix metalloproteinase inhibitor Ro31-9790

Schwann cell plasminogen activator is regulated by neurons

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