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Huang, Shan
Publications (10 of 11) Show all publications
Nilsson Ekdahl, K., Huang, S., Nilsson, B. & Teramura, Y. (2016). Complement inhibition in biomaterial- and biosurface-induced thromboinflammation. Seminars in Immunology, 28(3), 268-277
Open this publication in new window or tab >>Complement inhibition in biomaterial- and biosurface-induced thromboinflammation
2016 (English)In: Seminars in Immunology, ISSN 1044-5323, E-ISSN 1096-3618, Vol. 28, no 3, p. 268-277Article in journal (Refereed) Published
Abstract [en]

Therapeutic medicine today includes a vast number of procedures involving the use of biomaterials, transplantation of therapeutic cells or cell clusters, as well as of solid organs. These treatment modalities are obviously of great benefit to the patient, but also present a great challenge to the innate immune system, since they involve direct exposure of non-biological materials, cells of non-hematological origin as well as endothelial cells, damaged by ischemia-perfusion in solid organs to proteins and cells in the blood. The result of such an exposure may be an inappropriate activation of the complement and contact/kallikrein systems, which produce mediators capable of triggering the platelets and PMNs and monocytes, which can ultimately result in thrombotic and inflammatory (i.e., a thrombo-inflammatory) response to the treatment modality. In this concept review, we give an overview of the mechanisms of recognition within the innate immunity system, with the aim to identify suitable points for intervention. Finally, we discuss emerging and promising techniques for surface modification of biomaterials and cells with specific inhibitors in order to diminish thromboinflammation and improve clinical outcome.

National Category
Immunology in the medical area Microbiology in the medical area
Research subject
Biomedical Sciences, Immunology; Ecology, Microbiology
Identifiers
urn:nbn:se:lnu:diva-52312 (URN)10.1016/j.smim.2016.04.006 (DOI)000381845600007 ()27211838 (PubMedID)2-s2.0-84971261486 (Scopus ID)
Available from: 2016-04-28 Created: 2016-04-28 Last updated: 2018-11-16Bibliographically approved
Ran, B., Huang, S. & Henriksson, G. (2016). Isolation of exceedingly low oxygen consuming fungal strains able to utilize lignin as carbon source. Cellulose Chemistry and Technology, 50(7-8), 811-817
Open this publication in new window or tab >>Isolation of exceedingly low oxygen consuming fungal strains able to utilize lignin as carbon source
2016 (English)In: Cellulose Chemistry and Technology, ISSN 0576-9787, Vol. 50, no 7-8, p. 811-817Article in journal (Refereed) Published
Abstract [en]

Lignin biodegradation is normally related to aerobic microorganisms, and it is often claimed that microbes do not metabolize lignin as a carbon source. In this work, several fungal strains were isolated from the sediment of a small stream located in a forest and tested on agar plates with lignin as the only carbon source. All identified strains were Ascomycetes, Penicillium spinulosum, Pseudeurotium bakeri and Galactomyces geotrichum. When cultivated in shaking flasks with lignosulphonate as a carbon source, the lignin was consumed, and cell free culture filtrates appeared to depolymerize lignosulphonate to some extent. It is suggested that the strains detected are part of a symbiotic community and live in a microbiological niche in which they are able to utilize lignin residues left from brown rot and humus having extremely low oxygen content.

Keywords
carbon source, extracellular enzymes, extremely low oxygen content, lignin biodegradation, soil microorganisms
National Category
Biological Sciences Chemical Sciences
Research subject
Natural Science, Chemistry
Identifiers
urn:nbn:se:lnu:diva-60808 (URN)000392468700011 ()
Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2017-11-29Bibliographically approved
Huang, S., Engberg, A. E., Jonsson, N., Sandholm, K., Nicholls, I. A., Mollnes, T. E., . . . Nilsson Ekdahl, K. (2016). Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.. Biomaterials, 77, 111-119
Open this publication in new window or tab >>Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.
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2016 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 77, p. 111-119Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models.

METHODS: Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release.

RESULTS: Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG.

CONCLUSIONS: A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Biomaterials, Complement system, Contact system, FXII, In vitro screening
National Category
Biomaterials Science
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-47390 (URN)10.1016/j.biomaterials.2015.10.067 (DOI)000367118200010 ()26584351 (PubMedID)2-s2.0-84949221849 (Scopus ID)
Available from: 2015-11-24 Created: 2015-11-24 Last updated: 2018-11-16Bibliographically approved
Huang, S., Sandholm, K., Nilsson, B. & Nilsson Ekdahl, K. (2015). iC3 generation elicited by the presence of ammonia and urea in human plasma. Paper presented at 15th European Meeting on Complement in Human Disease (EMCHD), JUN 27-30, 2015, Uppsala, SWEDEN. Molecular Immunology, 67(1), 145-145
Open this publication in new window or tab >>iC3 generation elicited by the presence of ammonia and urea in human plasma
2015 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 67, no 1, p. 145-145Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-45774 (URN)000357144100088 ()
Conference
15th European Meeting on Complement in Human Disease (EMCHD), JUN 27-30, 2015, Uppsala, SWEDEN
Available from: 2015-08-20 Created: 2015-08-19 Last updated: 2018-11-16Bibliographically approved
Huang, S. (2015). Interaction between biomaterials and innate immunity with clinical implications. (Doctoral dissertation). Växjö: Linnaeus University Press
Open this publication in new window or tab >>Interaction between biomaterials and innate immunity with clinical implications
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Today there is an increasing clinical demand and expectation of patients for biomaterials, which underscores the importance of discovering the correlations between biomaterials and biological systems, especially blood. When an artificial material makes contact with blood, the first event is a rapid adsorption of plasma protein on the material surface, on top of which the innate immune system is triggered, with potentially detrimental consequences. The work presented in this thesis, reported in four papers, was designed to investigate complications associated with (a) biomaterial-induced immune systems, including activation mechanisms and crosstalk between cascades on the biomaterial surface, and with (b) clinical investigations.

In Paper I and Paper II, a series of studies led to the development of a direct prediction of the subsequent biological events based on the pattern of initially bound proteins. A reciprocal relationship was demonstrated between activation of the contact system and the complement system when they were induced on artificial material surfaces. Based on these studies, a robust and simple method for biocompatibility testing was proposed and validated, yielding high specificity and sensitivity when compared to today’s gold standard. Paper III investigated biomaterial-induced activation of complement and leukocytes in dialysis treatment-related conditions. The results suggested that citrate is more biocompatible than the conventionally used acetate. This reduction in activation could be further enhanced with higher citrate concentrations, suggesting that dialysis fluid containing citrate is a promising alternative to acetate dialysis fluid. Paper IV investigated complement initiation mechanisms with clinical implications. An experimental system was set up to revisit the initiation of the complement alternative pathway, and correlations were found between chaotropic or nucleophilic agents and iC3 generation under physiologically relevant conditions. A clinical study of hepatic encephalopathy patients indicated a direct correlation between elevated plasma ammonia and iC3 formation, as well as with complement activation in vivo

Taken together, these studies have provided a model for a robust biomaterial test and have investigated biomaterial-induced complications in the fluid phase in clinically related conditions; furthermore, the basic mechanisms of complement activation have been dissected in relation to disease symptoms.

Keywords: Complement system, contact system, blood, biomaterials, biocompatibility, in vitro screening, iC3, dialysis

Place, publisher, year, edition, pages
Växjö: Linnaeus University Press, 2015
Series
Linnaeus University Dissertations ; 236/2015
Keywords
Complement system, contact system, blood, biomaterials, biocompatibility, in vitro screening, iC3, dialysis
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:lnu:diva-47391 (URN)978-91-87925-87-0 (ISBN)
Public defence
2015-12-18, N2007, Smålandsgatan 24, Kalmar, 09:30 (English)
Opponent
Supervisors
Available from: 2015-11-26 Created: 2015-11-24 Last updated: 2015-11-26Bibliographically approved
Huang, S., Sandholm, K., Jonsson, N., Nilsson, A., Wieslander, A., Grundström, G., . . . Nilsson Ekdahl, K. (2015). Low concentrations of citrate reduce complement and granulocyte activation in vitro in human blood. Clinical Kidney Journal, 8(1), 31-37
Open this publication in new window or tab >>Low concentrations of citrate reduce complement and granulocyte activation in vitro in human blood
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2015 (English)In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 1, p. 31-37Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:The use of acetate in haemodialysis fluids may induce negative effects in patients including nausea and increased inflammation. Therefore, haemodialysis fluids where acetate is substituted with citrate have recently been developed. In this study, we investigated the biocompatibility of citrate employing concentrations used in haemodialysis.

METHODS:The effects of citrate and acetate were investigated in human whole blood in vitro under conditions promoting biomaterial-induced activation. Complement activation was measured as generation of C3a, C5a and the sC5b-9 complex, and granulocyte activation as up-regulation of CD11b expression. For the experimental set-up, a mathematical model was created to calculate the concentrations of acetate and citrate attained during haemodialysis.

RESULTS:Citrate reduced granulocyte activation and did not induce higher complement activation compared with acetate at concentrations attained during haemodialysis. Investigating different citrate concentrations clearly showed that citrate is a potent complement inhibitor already at low concentrations, i.e. 0.25 mM, which is comparable with concentrations detected in the blood of patients during dialysis with citrate-containing fluids. Increased citrate concentration up to 6 mM further reduced the activation of C3a, C5a and sC5b-9, as well as the expression of CD11b.

CONCLUSIONS:Our results suggest that citrate is a promising substitute for acetate for a more biocompatible dialysis, most likely resulting in less adverse effects for the patients.

National Category
Immunology in the medical area Urology and Nephrology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-40430 (URN)10.1093/ckj/sfu127 (DOI)25713707 (PubMedID)2-s2.0-84928381906 (Scopus ID)
Available from: 2015-02-25 Created: 2015-02-25 Last updated: 2018-11-16Bibliographically approved
Engberg, A. E., Nilsson, P. H., Huang, S., Fromell, K., Hamad, O. A., Mollnes, T. E., . . . Nilsson Ekdahl, K. (2015). Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma. Biomaterials, 36, 55-65
Open this publication in new window or tab >>Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
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2015 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, p. 55-65Article in journal (Refereed) Published
Abstract [en]

Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. (C) 2014 Elsevier Ltd. All rights reserved.

Keywords
Biomaterials, C4 binding protein (C4BP), Complement, Cytokines, Inflammation, In vitro screening
National Category
Immunology Biomaterials Science
Research subject
Chemistry, Organic Chemistry; Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-39124 (URN)10.1016/j.biomaterials.2014.09.011 (DOI)000345728200006 ()2-s2.0-84921965003 (Scopus ID)
Available from: 2015-01-15 Created: 2015-01-15 Last updated: 2018-11-02Bibliographically approved
Hancock, V., Huang, S., Nilsson, A., Grundstrom, G. & Nilsson Ekdahl, K. (2013). Citrate reduces complement and leukocyte activation in vitro in human blood. Paper presented at 50th European-Renal-Association - European-Dialysis-and-Transplant-Association Congress, MAY 18-21, 2013, Istanbul, TURKEY. Nephrology, Dialysis and Transplantation, 28, 207-208
Open this publication in new window or tab >>Citrate reduces complement and leukocyte activation in vitro in human blood
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2013 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 28, p. 207-208Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-27569 (URN)000319498201135 ()
Conference
50th European-Renal-Association - European-Dialysis-and-Transplant-Association Congress, MAY 18-21, 2013, Istanbul, TURKEY
Available from: 2013-07-17 Created: 2013-07-17 Last updated: 2017-12-06Bibliographically approved
Engberg, A. E., Nilsson, P. H., Sandholm, K., Huang, S., Mollnes, T. E., Nicholls, I. A., . . . Nilsson Ekdahl, K. (2013). The ratio between C4 and C4BP adsorbed to artificial materials is a new predictor for biocompatibility. Paper presented at 14th European Meeting on Complement in Human Disease, AUG 17-21, 2013, Jena, GERMANY. Molecular Immunology, 56(3), 309-309
Open this publication in new window or tab >>The ratio between C4 and C4BP adsorbed to artificial materials is a new predictor for biocompatibility
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2013 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 56, no 3, p. 309-309Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-29195 (URN)10.1016/j.molimm.2013.05.194 (DOI)000323019700189 ()
Conference
14th European Meeting on Complement in Human Disease, AUG 17-21, 2013, Jena, GERMANY
Available from: 2013-10-08 Created: 2013-10-03 Last updated: 2018-11-16Bibliographically approved
Huang, S., Nilsson, P. H., Sandholm, K., Elmlund, L., Nicholls, I. A. & Nilsson Ekdahl, K. (2012). Regulation of complement in whole blood by heparin molecularly imprinted polymer particles. Immunobiology, 217(11), 1199-1199
Open this publication in new window or tab >>Regulation of complement in whole blood by heparin molecularly imprinted polymer particles
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2012 (English)In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 217, no 11, p. 1199-1199Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-23357 (URN)10.1016/j.imbio.2012.08.200 (DOI)000311187800212 ()
Available from: 2013-01-09 Created: 2013-01-09 Last updated: 2017-12-06Bibliographically approved
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