The potentiation of human C1-inhibitor by dextran sulphate is transient in vivo: studies in a rat model
In: International immunopharmacology, Jg. 1 (2001), Heft 8, S. 1583-1595
academicJournal
- print, 46 ref
Zugriff:
Cl-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-Inh function 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 μM) inhibited C1s in rat plasma 55-fold faster in the presence of dextran sulphate (15 kDa, 5 μM). To study the stability of the complex in vivo, rats were given a mixture of Cl-lnh (10 mg/kg) and dextran sulphate (3 mg/kg). Cl-lnh activity during 5 h 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 C 1-Inh, lasting for 60-90 min. 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.
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The potentiation of human C1-inhibitor by dextran sulphate is transient in vivo: studies in a rat model
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Autor/in / Beteiligte Person: | BOS, Ineke G. A. C ; VAN MIERLO, Gerard J ; BLEEKER, Wim K ; RIGTER, Gemma M. M ; TE VELTHUIS, Henk ; DICKNEITE, Gerhard ; ERIK HACK, C |
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Zeitschrift: | International immunopharmacology, Jg. 1 (2001), Heft 8, S. 1583-1595 |
Veröffentlichung: | Amsterdam: Elsevier, 2001 |
Medientyp: | academicJournal |
Umfang: | print, 46 ref |
ISSN: | 1567-5769 (print) |
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