A novel mechanism of liver allograft rejection facilitated by antibodies to liver sinusoidal endothelial cells†

Sumitran–Holgersson, Suchitra; Ge, Xiaowen; Karrar, Azza; Xu, Bo; Nava, Stefano; Broomé, Ulrika; Nowak, G.; Ericzon, Bo‐Göran

doi:10.1002/hep.20434

Cited by 36 publications

(38 citation statements)

References 32 publications

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“…Each population was further characterized by flow cytometry, as described earlier, 16 using an array of antibodies to specific markers expressed on monocytes and endothelial cells (Table 1). FITC-conjugated acetylated low-density lipoprotein (AcLDL) (Molecular Probes, Eugene, OR), antibodies to VWF (DakoPatts, Glostrup, Denmark), ␣-actin, fibroblast (Serotec), and ulex europaeus (Sigma, Stockholm, Sweden) were used.…”

Section: Phenotyping and Cell Cultivationmentioning

confidence: 99%

Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity

Elsheikh

Uzunel

et al. 2005

Blood

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106

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The monocyte population in blood is considered a possible source of endothelial precursors. Because endothelial-specific receptor tyrosine kinases act as regulators of endothelial cell function, we investigated whether expression of the vascular endothelial growth factor receptor-2 (VEGFR-2) on monocytes is important for their endothelial-like functional capacity. Peripheral-blood monocytes expressing vascular endothelial growth factor receptor-2 (VEGFR-2), or CD14 ؉ /VEGFR-2 ؉ , were isolated, and their phenotypic, morphologic, and functional capacities were compared with those of monocytes nega-

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Section: Phenotyping and Cell Cultivationmentioning

confidence: 99%

Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity

Elsheikh

Uzunel

et al. 2005

Blood

Self Cite

106

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“…37 There is also a report suggesting that antibodies against sinusoidal cells can be related to rejection episodes. 38 Although our current protocol of C4d staining using paraffinembedded sections did not always demonstrate sinusoidal endothelial staining, perivenular staining was observed in crossmatch-positive patients. Considering these facts, crossmatch-positive humoral rejection may be characterized by more widely distributed C4d deposition than the usual acute 'cellular' rejection or ABO-incompatible humoral rejection.…”

Section: C4d In Liver Transplantationmentioning

confidence: 63%

Significance of C4d staining in ABO-identical/compatible liver transplantation

et al. 2007

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Complement degradation product C4d has become an important marker of humoral or antibody-mediated rejection in renal and heart allograft biopsies. Although there have been several reports on the detection of C4d in liver allografts, the significance of C4d in liver transplantation and its relationship with humoral rejection are still not clear. We investigated the frequency and pattern of C4d staining in liver allograft biopsies with reference to preoperative lymphocyte crossmatch tests, which detect donor-reactive lymphocyte antibody. Survival rates at 5 years were 77% for crossmatch-negative patients and 53% for crossmatch-positive patients (P ¼ 0.009). In crossmatch-negative patients, reproducible positive staining was obtained in 28 of 86 (33%) biopsies taken within 90 days after transplantation and 33 of 96 (34%) biopsies 90 days or after transplantation. Most C4d staining was observed in the portal areas, and no clear correlation was observed between C4d positivity and histological diagnosis. In crossmatch-positive patients, 9 of 11 (82%) biopsies showed positivity for C4d. C4d stained perivenular areas as well as portal areas. Histology of crossmatch-positive patients included acute rejection and cholangitis, but did not include periportal changes that were seen in humoral rejection in ABO-incompatible liver transplantation. In summary, focal C4d deposition was seen in various types of liver allograft injury and had little clinical impact on crossmatch-negative patients, but extensive C4d staining in crossmatch-positive patients may be associated with humoral rejection and poor graft survival.

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“…2,3 The human sinusoidal endothelium does not constitutively express HLA class II or co-stimulatory molecules 38 ; however, other properties of the endothelium, such as the high capacity for antigen uptake and direct access to circulating lymphocytes, may enable it to contribute to the unique immunological function of the liver.…”

Section: Discussionmentioning

confidence: 99%

FasL Expression in Hepatic Antigen-Presenting Cells and Phagocytosis of Apoptotic T Cells by FasL+ Kupffer Cells Are Indicators of Rejection Activity in Human Liver Allografts

Miyagawa‐Hayashino

Tsuruyama

Egawa

et al. 2007

The American Journal of Pathology

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JapanFas-Fas ligand (FasL) interaction and apoptosis are important in the mechanism of allograft rejection. However, the interaction between donor and recipient cells, specifically focusing on antigen-presenting cells (APCs), under various conditions is poorly understood in human liver allografts. FasL expression on APCs, its association with apoptosis, and the origin of apoptotic lymphocytes in human liver allografts were assessed by immunohistochemistry and in situ hybridization. We found increased expression of FasL on Kupffer cells (KCs) and endothelium in acute cellular rejection (n ‫؍‬ 20) and to lesser extent in chronic rejection (n ‫؍‬ 6) and septic cholangitis (n ‫؍‬ 5) compared with stable grafts and normal controls. In addition, the graft specificity of infiltrating T cells was confirmed by polymerase chain reaction examination of T-cell receptor-␥ loci. T-cell apoptosis occurred at a higher rate in acute cellular rejection than in chronic rejection or septic cholangitis. The number of apoptotic bodies derived from recipient lymphocytes correlated with the severity of rejection and was reversed by treatment.

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A novel mechanism of liver allograft rejection facilitated by antibodies to liver sinusoidal endothelial cells†

Cited by 36 publications

References 32 publications

Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity

Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity

Significance of C4d staining in ABO-identical/compatible liver transplantation

FasL Expression in Hepatic Antigen-Presenting Cells and Phagocytosis of Apoptotic T Cells by FasL+ Kupffer Cells Are Indicators of Rejection Activity in Human Liver Allografts

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