Partial Suppression of Experimental Allergic Encephalomyelitis With Heparin

Chelmicka-Szorc, Ewa; Arnason, Barry G. W.

doi:10.1001/archneur.1972.00490140057009

Cited by 29 publications

(17 citation statements)

References 24 publications

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“…Heparin has been shown previously by others to act as an antiinflammatory agent effective in modulating EAE (15) or preventing delayed-type hypersensitivity (16). It was also shown to influence the traffic oflymphocytes (17).…”

Section: Discussionmentioning

confidence: 96%

Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins.

Lider

Baharav²,

Mekori³

et al. 1989

J. Clin. Invest.

190

127

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Section: Discussionmentioning

confidence: 96%

Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins.

Lider

Baharav²,

Mekori³

et al. 1989

J. Clin. Invest.

190

127

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show abstract

“…NPGB, an inhibitor of plasminogen activator, has been shown to inhibit myelin breakdown in vitro in the presence of plasminogen and macrophage supernatant (Cammer et al, 19781, and to suppress clinical and histological signs of EAE (Brosnan et al, 1980). Polylysine, first shown by Chelmicka-Szorc and Arnason (1975) to suppress EAE in guinea pigs, was also effective in rats, presumably acting as a basic protein competitor for proteases (Smith and Amaducci, 1982). The rhein compounds that are derived from rhubarb are inhibitors of several proteases, including trypsin, carboxypeptidase A, elastase, and pepsin (Raimondi et al, 1982), although these compounds also have other effects (Kean et al, 1970).…”

Section: E Smith Et Almentioning

confidence: 99%

DNA Changes in Spinal Cords of Rats with Experimental Allergic Encephalomyelitis

Smith

Somera

Saldivar

et al. 1984

Journal of Neurochemistry

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DNA levels were measured in the spinal cords of Lewis rats during the development of and recovery from experimental allergic encephalomyelitis (EAE). Spinal cord DNA was first increased 11 days after immunizing the rats with guinea pig myelin and rose to levels four times that of the Freund's adjuvant controls at day 14, then subsided after day 22. Spinal cord DNA was still 150% of control levels 60 days after immunization. These DNA changes were compared with fluctuations in spinal cord acid proteinase in the same animals. Acid proteinase activity in EAE spinal cord increased later than the rise in DNA and attained a level of 170% of control at days 15-17, then subsided. Spinal cord DNA was higher in rats immunized with whole myelin than in those administered equivalent amounts of purified myelin basic protein. Furthermore DNA was higher in spinal cords of rats immunized with a larger dose of myelin (1.0 mg) than with a lower amount (0.5 mg). Various protease inhibitors including pepstatin, nitrophenyl p-guanidino benzoate, polylysine, and dipropionyl rhein, previously shown to protect Lewis rats against EAE, suppressed the increase of DNA in the spinal cord. Measurement of DNA increases in the spinal cord of EAE animals provides a convenient reproducible measurement of the severity of inflammation in the CNS and provides an objective criterion for assessment of the efficacy of various agents screened as possible therapeutic treatment for multiple sclerosis.

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“…It was already known that lysine residues are critical for GA prevention in experimental autoimmune encephalomyelitis (EAE) (13), an animal model for multiple sclerosis. The simpler poly L-lysine can also prevent EAE in guinea pigs (14). Hence, the positively charged residues of GA may play an important role in its pharmacological mode-of-action, but insight on mechanisms relating the requirement of positive charge to its immunomodulatory effects are lacking.…”

Section: Introductionmentioning

confidence: 99%

The random co-polymer glatiramer acetate rapidly kills primary human leukocytes through sialic-acid-dependent cell membrane damage

Christiansen

Zhang

Juul-Madsen

et al. 2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The formulation glatiramer acetate (GA) is widely used in therapy of multiple sclerosis. GA consists of random copolymers of four amino acids, in ratios that produce a predominantly positive charge and an amphipathic character. With the extraordinary complexity of the drug, several pharmacological modes-of-action were suggested, but so far none, which rationalizes the cationicity and amphipathicity as part of the mode-of-action. Here, we report that GA rapidly kills primary human T lymphocytes and, less actively, monocytes. LL-37 is a cleavage product of human cathelicidin with important roles in innate immunity. It shares the positive charge and amphipathic character of GA, and, as shown here, also the ability to kill human leukocyte. The cytotoxicity of both compounds depends on sialic acid in the cell membrane. The killing was associated with the generation of CD45+ debris, derived from cell membrane deformation. Nanoparticle tracking analysis confirmed the formation of such debris, even at low GA concentrations. Electric cellsubstrate impedance sensing measurements also recorded stable alterations in T lymphocytes following such treatment. LL-37 forms oligomers through weak hydrophobic contacts, which is critical for the lytic properties. In our study, SAXS showed that GA also forms this type of contacts.Taken together, our study offers new insight on the immunomodulatory mode-of-action of positively charged co-polymers. The comparison of LL-37 and GA highlights a consistent requirement of certain oligomeric and chemical properties to support cytotoxic effects of cationic polymers targeting human leukocytes.

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Partial Suppression of Experimental Allergic Encephalomyelitis With Heparin

Abstract: (27:153-158, 1972)

Cited by 29 publications

References 24 publications

Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins.

Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins.

DNA Changes in Spinal Cords of Rats with Experimental Allergic Encephalomyelitis

The random co-polymer glatiramer acetate rapidly kills primary human leukocytes through sialic-acid-dependent cell membrane damage

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