Interactions between platelets and complement with implications for the regulation at surfaces

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Fältnamn	Indikatorer	Metadata
000		05807nam a2200613 4500
001		oai:DiVA.org:lnu-18321
003		SwePub
008		120413s2012 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
020		a 9789186983468q print
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-183212 URI
040		a (SwePub)lnu
041		a engb eng
042		9 SwePub
072	7	a vet2 swepub-contenttype
072	7	a dok2 swepub-publicationtype
100	1	a Nilsson, Per H.,d 1980-u Linnéuniversitetet,Institutionen för naturvetenskap, NV4 aut0 (Swepub:lnu)enipe
245	1 0	a Interactions between platelets and complement with implications for the regulation at surfaces
264	1	a Växjö, Kalmar :b Linnaeus University Press,c 2012
300		a 87 s.
338		a electronic2 rdacarrier
490	0	a Linnaeus University Dissertations ;v 83
520		a Disturbances of host integrity have the potential to evoke activation of innate immunologic and hemostatic protection mechanisms in blood. Irrespective of whether the activating stimulus is typically immunogenic or thrombotic, it will generally affect both the complement system and platelets to a certain degree. The theme of this thesis is complement and platelet activity, which is intersected in all five included papers. The initial aim was to study the responses and mechanisms of the complement cascade in relation to platelet activation. The secondary aim was to use an applied approach to regulate platelets and complement on model biomaterial and cell surfaces. Complement activation was found in the fluid phase in response to platelet activation in whole blood. The mechanism was traced to platelet release of stored chondroitin sulfate-A (CS-A) and classical pathway activation via C1q. C3 was detected at the platelet surface, though its binding was independent of complement activation. The inhibitors factor H and C4-binding protein (C4BP) were detected on activated platelets, and their binding was partly dependent on surface-exposed CS-A. Collectively, these results showed that platelet activation induces inflammatory complement activation in the fluid phase. CS-A was shown to be a central molecule in the complement-modulatory functions of platelets by its interaction with C1q, C4BP, and factor H.Platelet activation and surface adherence were successfully attenuated by conjugating an ADP-degrading apyrase on a model biomaterial. Only minor complement regulation was seen, and was therefore targeted specifically on surfaces and cells by co-immobilizing a factor H-binding peptide together with the apyrase. This combined approach led to a synchronized inhibition of both platelet and complement activation at the interface of biomaterials/xenogeneic cells and blood.In conclusion, here presents a novel crosstalk-mechanism for activation of complement when triggering platelets, which highlights the importance of regulating both complement and platelets to lower inflammatory events. In addition, a strategy to enhance the biocompatibility of biomaterials and cells by simultaneously targeting ADP-dependent platelet activation and the alternative complement C3-convertase is proposed.
650	7	a NATURVETENSKAPx Biologix Immunologi0 (SwePub)106052 hsv//swe
650	7	a NATURAL SCIENCESx Biological Sciencesx Immunology0 (SwePub)106052 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Biomaterialvetenskap0 (SwePub)304032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Biomaterials Science0 (SwePub)304032 hsv//eng
650	7	a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650	7	a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng
653		a complement system (activation
653		a regulation)
653		a platelets (activation
653		a regulation)
653		a biomaterials
653		a biocompatibility
653		a chondroitin sulfate-A
653		a apyrase
653		a C1q
653		a C3
653		a factor H
653		a C4BP
653		a ADP
653		a Biomedical Sciences
653		a Biomedicinsk vetenskap
700	1	a Nilsson Ekdahl, Kristina,c Professoru Linnéuniversitetet,Institutionen för naturvetenskap, NV4 ths
700	1	a Lambris, John,c Professoru Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA4 ths
700	1	a Nicholls, Ian,c Professoru Linnéuniversitetet,Institutionen för naturvetenskap, NV4 ths
700	1	a Ghebrehiwet, Berhane,c Professoru Department of Medicine, Stony Brook University, USA4 opn
710	2	a Linnéuniversitetetb Institutionen för naturvetenskap, NV4 org
856	4	u mailto:lnupress@lnu.se?subject=Order: Nilsson, Interactions between platelets and complement with implications for the regulation at surfaces&body=Publication: Interactions between platelets and complement with implications for the regulation at surfaces %0D%0AAuthor: Nilsson, Per H.%0D%0APrice per copy: SEK 250 + VAT and postage%0D%0A%0D%0ANo of Copies: %0D%0ACustomer name: %0D%0ABilling address: %0D%0APostal address:y Buy Book (SEK 250 + VAT and postage) lnupress@lnu.se
856	4	u https://lnu.diva-portal.org/smash/get/diva2:515586/FULLTEXT01.pdfx primaryx Raw objecty fulltext
856	4	u https://lnu.diva-portal.org/smash/get/diva2:515586/PREVIEW01.jpgx Previewy preview image
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-18321

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