Blocking of human anti-pig xenoantibodies by soluble GAL alpha 1-3Gal and Gal alpha 1-2Gal disaccharides; studies in a pig kidney in vitro perfusion model.

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Magnusson, Stefan (author)

Blocking of human anti-pig xenoantibodies by soluble GAL alpha 1-3Gal and Gal alpha 1-2Gal disaccharides; studies in a pig kidney in vitro perfusion model.

Article/chapterEnglish2000

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2000

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LIBRIS-ID:oai:gup.ub.gu.se/211617
https://gup.ub.gu.se/publication/211617URI

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Language:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Depletion of anti-pig xenoantibodies reduces cell cytotoxicity of human serum to pig endothelial cells and lymphocytes. The aim of this study was to test, in a pig kidney xenoperfusion model, the ability of soluble alpha Gal terminated disaccharides to prevent the hyperacute rejection process in an organ. Porcine kidneys were perfused with whole human blood lacking saccharide and blood supplemented with Gal alpha 1-3GAL, Gal alpha 1-2Gal and lactose. Parameters evaluated were, urine production, renal blood flow, vascular resistance, renal clearance, blood cell counts, xenoantibody titers, complement activation and histopathology. The blood flow was higher in the Gal alpha 1-3Gal (155 +/- 31 ml/min x 100 g-1 kidney tissue) group compared to Gal alpha 1-2Gal (138 +/- 16), lactose (92 +/- 78) and controls (69 +/- 16), When calculated as percent of the blood flow value at 1 min, the blood flow at 30 min was 157% for the Gal alpha 1-3Gal and for 187% the Gal alpha 1-2Gal. The corresponding values for the lactose and control groups were 102% and 74%, respectively. Urine production in the lactose/control groups was lower (0.7 ml/min x 100 g-1 kidney tissue) compared to Gal alpha 1-3Gal (3.0) and Gal alpha 1-2Gal (3.7). Urine sodium excretion was reduced in the lactose/control groups, compared to the Gal alpha alpha 1-groups during the perfusions. An increase in urine potassium excretion was found in the Gal alpha alpha 1-groups while a reduction occurred in the lactose/control experiments. An initial 40-50% reduction in platelet count was observed in all groups while the leukocyte count showed a continuous decrease. Immunohistochemistry revealed less deposition of IgM, IgG, C3 and C1 q in the Gal alpha alpha 1-saccharide groups compared to the lactose/control groups. Soluble Gal alpha a1-disaccharides improved both functional and histological parameters. However, significant pathological changes were still present indicating that this approach to inhibit HAR must be used in combination with additional therapeutic approaches such as solid phase xenoantibody immunoadsorption and blocking of complement activation.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kirurgi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Surgery hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
Animals
Antibodies
Heterophile
blood
immunology
Antigen-Antibody Complex
analysis
Disaccharides
pharmacology
Diuresis
drug effects
Female
Graft Rejection
prevention & control
Humans
Immunosuppressive Agents
pharmacology
Kidney
blood supply
drug effects
immunology
pathology
physiopathology
Lactose
pharmacology
Leukocyte Count
Male
Natriuresis
drug effects
Perfusion
Potassium
urine
Renal Circulation
drug effects
Swine
Vascular Resistance
drug effects

Added entries (persons, corporate bodies, meetings, titles ...)

Strokan, V (author)
Mölne, Johan,1958Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin , Avdelningen för patologi,Institute of Laboratory Medicine, Dept of Pathology(Swepub:gu)xmolnj (author)
Nilsson, K (author)
Rydberg, Lennart,1944Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin, Avdelningen för klinisk kemi/transfusionsmedicin,Institute of Laboratory Medicine, Dept of Clinical Chemistry/Transfusion Medicine(Swepub:gu)xrydle (author)
Breimer, Michael,1951Gothenburg University,Göteborgs universitet,Institutionen för de kirurgiska disciplinerna, Avdelningen för kirurgi,Institute of Surgical Sciences, Department of Surgery(Swepub:gu)xbremi (author)
Göteborgs universitetInstitutionen för laboratoriemedicin , Avdelningen för patologi (creator_code:org_t)

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In:Transplant international : official journal of the European Society for Organ Transplantation13:6, s. 402-120934-0874

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