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Titolo:
The potentiation of human C1-inhibitor by dextran sulphate is transient invivo: studies in a rat model
Autore:
Bos, IGAC; van Mierlo, GJ; Bleeker, WK; Rigter, GMM; Velthuis, HT; Dickneite, G; Hack, CE;
Indirizzi:
Univ Amsterdam, Acad Med Ctr, Dept Immunopathol, CLB, NL-1066 CX Amsterdam, Netherlands Univ Amsterdam Amsterdam Netherlands NL-1066 CX X Amsterdam, Netherlands Univ Amsterdam, Acad Med Ctr, Expt & Clin Immunol Lab, NL-1066 CX Amsterdam, Netherlands Univ Amsterdam Amsterdam Netherlands NL-1066 CX X Amsterdam, Netherlands Aventis Behring, Marburg, Germany Aventis Behring Marburg GermanyAventis Behring, Marburg, Germany
Titolo Testata:
INTERNATIONAL IMMUNOPHARMACOLOGY
fascicolo: 8, volume: 1, anno: 2001,
pagine: 1583 - 1595
SICI:
1567-5769(200108)1:8<1583:TPOHCB>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
C1 ESTERASE INHIBITOR; CLASSICAL COMPLEMENT PATHWAY; C1-ESTERASE INHIBITOR; HUMAN-PLASMA; MONOCLONAL-ANTIBODY; PROTEASE INHIBITORS; SERINE-PROTEASE; 1ST COMPONENT; CL-INHIBITOR; FACTOR-XIIA;
Keywords:
complement; Cl-Inh; inflammation; serpin; ELISA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Bos, IGAC Univ Amsterdam, Acad Med Ctr, Dept Immunopathol, CLB, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands Univ Amsterdam Plesmanlaan 125 Amsterdam Netherlands NL-1066 CX
Citazione:
I.G.A.C. Bos et al., "The potentiation of human C1-inhibitor by dextran sulphate is transient invivo: studies in a rat model", INT IMMUNO, 1(8), 2001, pp. 1583-1595

Abstract

C1-inhibitor (C1-Inh) is an important regulator of inflammatory reactions because it is a potent inhibitor of the contact and complement system. C1-Inh application in inflammatory disease is, however, restricted because of the high doses required. The glycosaminoglycan-like molecule dextran sulphate (DXS) enhances C1-Inhfunction in vitro. Hence, we investigated whether co-administration with dextran sulphate reduces the amount of C1-Inh required, through enhancement in vivo. C1-Inh potentiation was measured in a newly developed C1s-inactivation assay that is based on activation of C4 by purified C1s. Activated C4 in rat plasma was quantified with a newly developed ELISA. Human C1-Inh (2.5 muM) inhibited Cls in rat plasma 55-fold faster in the presence of dextran sulphate (15 kDa, 5 muM). To study the stability of the complex in vivo, rats were given a mixture of C1-Inh (10 mg/kg) and dextran sulphate (3 mg/kg), C1-Inh activity during 5 It was analyzed ex vivo with the C1s inactivation assay. The noncovalent C1-Inh-dextran sulphate complex resulted in a transient enhancement of the inhibitory capacity of C1-Inh, lasting for 60-90min. Dextran sulphate did not affect plasma clearance of C1-Inh. We conclude that the enhanced inhibitory capacity of C1-Inh complexed to dextran sulphate is transient in vivo. Hence, co-administration of these compounds seems a feasible approach to achieve short-term inhibition of complement in vivo. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 03:21:56