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Human CMV infection of porcine endothelial cells increases adhesion receptor expression and human leukocyte recruitment

Ghielmetti, Maddalena
Millard, Anne-Laure
Haeberli, Lea
Bossart, Walter
Schneider, Marten K. J.
Mueller, Nicolas J.
Published in Transplantation. 2009, vol. 87, no. 12, p. 1792-1800
Abstract BACKGROUND: Potential xenozoonosis is a concern for the clinical application of xenotransplantation. Human cytomegalovirus (HCMV) is one of the most important pathogens in allotransplantation, but the consequences of HCMV cross-species infection of porcine xenografts are unknown. Therefore, we investigated the effects of HCMV infection of porcine endothelial cells (pEC) on cell surface molecule expression and human leukocyte recruitment. METHODS: Infection of pEC inoculated with untreated, UV-inactivated, or heparin-treated HCMV at a multiplicity of infection (MOI) of 1 was analyzed by immediate early (IE) antigen expression. Cell surface receptor expression was studied by flow cytometry on pEC bulk cultures and differentially on IE-positive and -negative pEC. Adhesion of human leukocytes was tested on pEC monolayers. pEC supernatants were analyzed for cytokine content, chemotactic activity, and stimulatory effect on resting secondary pEC cultures. RESULTS: At day 2 postinfection, IE staining was evident in 10% to 20% of HCMV-infected cells. Cell-surface expression of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) was upregulated in both IE-negative and -positive fractions of HCMV-infected pEC. In contrast, porcine major histocompatibility complex class I expression was upregulated in IE-negative cells, but reduced in IE-positive cells. The receptor alterations in the IE-negative fraction were mediated by pEC-derived soluble factors. The increased adhesion receptor expression was paralleled by enhanced human leukocyte chemotaxis and adhesion to infected pEC cultures. Pretreatment of HCMV with heparin, but not UV-inactivation, prevented adhesion-receptor modulation and reversed the increased adhesion and chemotaxis. CONCLUSIONS: After pig-to-human solid organ transplantation HCMV may infect and activate the porcine endothelium, rendering the xenograft more susceptible to human leukocyte recruitment and rejection.
Keywords AnimalsCell AdhesionCytokines/analysisCytomegalovirus/isolation & purification/pathogenicityCytomegalovirus Infections/pathology/*physiopathologyDisaccharides/deficiencyEndothelial Cells/cytology/physiology/*virologyFlow CytometryHumansLeukocytes/*physiology/virologyMembrane GlycoproteinsMembrane Proteins/*geneticsSwineTransplantation, Heterologous/adverse effectsZoonoses/transmission
PMID: 19543055
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Research group Laboratoire d'immunologie translationnelle (856)
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GHIELMETTI, Maddalena et al. Human CMV infection of porcine endothelial cells increases adhesion receptor expression and human leukocyte recruitment. In: Transplantation, 2009, vol. 87, n° 12, p. 1792-1800. doi: 10.1097/TP.0b013e3181a75a41 https://archive-ouverte.unige.ch/unige:19834

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Deposited on : 2012-04-23

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