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dc.contributor.authorCaldwell, Elizabeth E.O.
dc.contributor.authorAndreasen, Alan M.
dc.contributor.authorBlietz, Melinda A.
dc.contributor.authorSerrahn, Jill N.
dc.contributor.authorVandernoot, Victoria
dc.contributor.authorPark, Youmie
dc.contributor.authorYu, Guyong
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorWeiler, John M.
dc.identifier.citationHeparin Binding and Augmentation of C1 Inhibitor Activity, E.E.O.Caldwell, A.M. Andreason, M.A. Blietz, J. N. Serrahn, V. VanderNoot, R.J.Linhardt, J.M. Weiler, Archives in Biochemistry and Biophysics,361,215-222, 1999.
dc.descriptionArchives in Biochemistry and Biophysics, 361, 215-222
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractHeparin and other glycosaminoglycans have profound activity in vitro on the regulation of complement activity. The studies reported here examined the mechanism whereby heparin enhances C1 esterase inhibitor (C1INH) activity on C1 esterase (C1). The interaction of heparin and heparan sulfate with C1INH was first examined using surface plasmon resonance. Heparin was immobilized on a biosensor chip in two orientations, at its reducing end and in midchain, and heparan sulfate was immobilized at its reducing end. Heparin immobilized at its reducing end interacted with C1INH, giving an association constant (Ka) value of 1.43 x 10(7) M-1, whereas heparin immobilized in midchain afforded a Ka value of 7 x 10(6) M-1. No interaction between C1INH and heparan sulfate could be observed. Next, the augmentation of C1INH by heparin (Mr (av) 13,000), low-molecular-weight (LMW) heparin (Mr (av) 5000), and heparan sulfate (Mr (av) 11,000) was determined. C1INH alone was at least 10, 000 times more active in inhibiting fluid phase C1 compared with erythrocyte-bound C1 (EAC1). When C1 was in the fluid phase, both heparin and LMW heparin were relatively ineffective at augmenting C1INH activity on C1. In contrast, when C1 was present as EAC1, heparin augmented C1INH activity at all C1INH concentrations examined and LMW heparin was up to 1.3 times more effective than heparin. This augmentation only occurred when both C1INH and heparin were present together with the EAC1. Hence, although surface plasmon resonance shows that heparin binds to C1INH, heparin augmentation of C1INH activity appears to require a terniary complex in which cell bound C1 interacts with both heparin and C1INH. This is the first report of LMW heparin augmenting C1INH activity. Heparan sulfate neither interacted with C1INH nor did it augment C1INH activity.
dc.description.sponsorshipNational Institutes of Health
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofArchives of Biochemistry and Biophysics
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleHeparin Binding and Augmentation of C1 Inhibitor Activity
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)

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