| Autor: |
Bos IG; Department of Immunopathology, CLB and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, The Netherlands. I_Bos@clb.nl, van Mierlo GJ, Bleeker WK, Rigter GM, te Velthuis H, Dickneite G, Hack CE |
| Jazyk: |
angličtina |
| Zdroj: |
International immunopharmacology [Int Immunopharmacol] 2001 Aug; Vol. 1 (8), pp. 1583-95. |
| DOI: |
10.1016/s1567-5769(01)00073-x |
| Abstrakt: |
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-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 microM) inhibited C1s in rat plasma 55-fold faster in the presence of dextran sulphate (15 kDa, 5 microM). 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 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 C1-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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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