Search: onr:"swepub:oai:DiVA.org:lnu-105799" >
Combined blockade o...
Combined blockade of complement C5 and TLR co-receptor CD14 synergistically inhibits pig-to-human corneal xenograft induced innate inflammatory responses
-
- Islam, Rakibul (author)
- Oslo Univ Hosp, Norway;Univ Oslo, Norway
-
- Islam, Mohammad Mirazul (author)
- Massachusetts Eye & Ear, USA;Schepens Eye Res Inst, USA;Harvard Med Sch, USA
-
- Nilsson, Per H., 1980- (author)
- Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Avancerade material,Oslo Univ Hosp, Norway;Univ Oslo, Norway,Linnaeus Ctr Biomat Chem, BMC;HoRB
-
show more...
-
- Mohlin, Camilla, 1972- (author)
- Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Linnaeus Ctr Biomat Chem, BMC
-
- Hagen, Kjersti Thorvaldsen (author)
- Univ Oslo, Norway
-
- Paschalis, Eleftherios, I (author)
- Schepens Eye Res Inst, USA;Harvard Med Sch, USA
-
- Woods, Russell L. (author)
- Schepens Eye Res Inst, USA;Harvard Med Sch, USA
-
- Bhowmick, Sabuj Chandra (author)
- Univ Oslo, Norway
-
- Dohlman, Claes H. (author)
- Massachusetts Eye & Ear, USA;Harvard Med Sch, USA
-
- Espevik, Terje (author)
- Norwegian Univ Sci & Technol, Norway
-
- Chodosh, James (author)
- Massachusetts Eye & Ear, USA;Harvard Med Sch, USA
-
- Gonzalez-Andrades, Miguel (author)
- Massachusetts Eye & Ear, USA;Schepens Eye Res Inst, USA;Harvard Med Sch, USA;Reina Sofia Univ Hosp, Spain;Univ Cordoba, Spain
-
- Mollnes, Tom Eirik (author)
- Oslo Univ Hosp, Norway;Univ Oslo, Norway;Norwegian Univ Sci & Technol, Norway;Nordland Hosp, Norway;Univ Tromso, Norway
-
show less...
-
(creator_code:org_t)
- Elsevier, 2021
- 2021
- English.
-
In: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 127, s. 169-179
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://lnu.diva-por... (primary) (Raw object)
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Inadequate supplies of donor corneas have evoked an escalating interest in corneal xenotransplantation. However, innate immune responses contribute significantly to the mechanism of xenograft rejection. We hypothesized that complement component C5 and TLR co-receptor CD14 inhibition would inhibit porcine cornea induced innate immune responses. Therefore, we measured cytokine release in human blood, induced by three forms of corneal xenografts with or without inhibitors. Native porcine cornea (NPC) induced interleukins (IL-1 beta, IL-2, IL-6, IL-8, IL-1ra), chemokines (MCP-1, MIP-1 alpha, MIP-1 beta) and other cytokines (TNF, G-CSF, INF-gamma, FGF-basic). Decellularized (DPC) and gamma-irradiated cornea (g-DPC) elevated the release of those cytokines. C5-blockade by eculizumab inhibited all the cytokines except G-CSF when induced by NPC. However, C5-blockade failed to reduce DPC and g-DPC induced cytokines. Blockade of CD14 inhibited DPC-induced cytokines except for IL-8, MCP-1, MIP-1 alpha, and G-CSF, while it inhibited all of them when induced by g-DPC. Combined blockade of C5 and CD14 inhibited the maximum number of cytokines regardless of the xenograft type. Finally, by using the TLR4 specific inhibitor Eritoran, we showed that TLR4 activation was the basis for the CD14 effect. Thus, blockade of C5, when combined with TLR4 inhibition, may have therapeutic potential in pig-to-human corneal xenotransplantation. Statement of significance Bio-engineered corneal xenografts are on the verge of becoming a viable alternative to allogenic human donor-cornea, but the host's innate immune response is still a critical barrier for graft acceptance. By overruling this barrier, limited graft availability would no longer be an issue for treating corneal diseases. We showed that the xenograft induced inflammation is initiated by the complement system and toll-like receptor activation. Intriguingly, the inflammatory response was efficiently blocked by simultaneously targeting bottleneck molecules in the complement system (C5) and the TLR co-receptor CD14 with pharmaceutical inhibitors. We postulate that a combination of C5 and CD14 inhibition could have a great therapeutic potential to overcome the immunologic barrier in pig-to-human corneal xenotransplantation. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomaterialvetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomaterials Science (hsv//eng)
Keyword
- Xenotransplantation
- Cornea
- Decellularization
- Complement system
- Toll-like receptor
- Cytokine
- Regenerative medicine
- Biomaterial
- Immunologi
- Immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Islam, Rakibul
-
Islam, Mohammad ...
-
Nilsson, Per H., ...
-
Mohlin, Camilla, ...
-
Hagen, Kjersti T ...
-
Paschalis, Eleft ...
-
show more...
-
Woods, Russell L ...
-
Bhowmick, Sabuj ...
-
Dohlman, Claes H ...
-
Espevik, Terje
-
Chodosh, James
-
Gonzalez-Andrade ...
-
Mollnes, Tom Eir ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Immunology in th ...
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Medical Biotechn ...
-
and Biomaterials Sci ...
- Articles in the publication
-
Acta Biomaterial ...
- By the university
-
Linnaeus University