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Mediation of a non-...
Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles
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- Klapper, Yvonne (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala University
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- Hamad, Osama A. (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala University
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- Teramura, Yuji (författare)
- Uppsala universitet,Klinisk immunologi,Uppsala University
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- Leneweit, Gero (författare)
- Assoc Promot Canc Therapy, Germany
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- Nienhaus, G. Ulrich (författare)
- Karlsruhe Inst Technol KIT, Germany
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- Ricklin, Daniel (författare)
- Univ Penn, USA
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- Lambris, John D. (författare)
- Univ Penn, USA
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- Nilsson Ekdahl, Kristina (författare)
- Uppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University,Linnaeus Ctr Biomat Chem, BMC,Klinisk immunologi
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- Nilsson, Bo (författare)
- Uppsala universitet,Klinisk immunologi,Uppsala University
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- Engelska.
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 35:11, s. 3688-3696
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Liposomes are becoming increasingly important as drug delivery systems, to target a drug to specific cells and tissues and thereby protecting the recipient from toxic effects of the contained drug. Liposome preparations have been described to activate complement. In this study, we have investigated complement activation triggered by neutral dimyristoyl-phosphocholine (DMPC) liposomes in human plasma and whole-blood systems. Incubation in plasma led to the generation of complement activation products (C3a and sC5b-9). Unexpectedly, investigations of surface-bound C3 revealed contact activated, conformationally changed C3 molecules on the liposomes. These changes were characterized by Western blotting with C3 monoclonal antibodies, and by incubating liposomes with purified native C3 and factors I and H. Quartz crystal microbalance analysis confirmed binding of C3 to planar DMPC surfaces. In addition, we demonstrated that DMPC liposomes bound to or were phagocytized by granulocytes in a complement-dependent manner, as evidenced by the use of complement inhibitors. In summary, we have shown that C3 is activated both by convertase-dependent cleavage, preferentially in the fluid phase, by mechanisms which are not well elucidated, and also by contact activation into C3(H2O) on the DMPC surface. In particular, this contact activation has implications for the therapeutic regulation of complement activation during liposome treatment. (C) 2013 Elsevier Ltd. All rights reserved.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- Liposome
- Complement
- Immune response
- Contact activation
- Immunologi
- Immunology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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