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. 2014:2014:582902.
doi: 10.1155/2014/582902. Epub 2014 Feb 10.

Capillary dilation and rarefaction are correlated with intracapillary inflammation in antibody-mediated rejection

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Capillary dilation and rarefaction are correlated with intracapillary inflammation in antibody-mediated rejection

Xue Li et al. J Immunol Res. 2014.

Abstract

Antibody-mediated rejection (ABMR) remains one of the major causes of graft loss after renal transplantation. It is dominated by endothelial damage in microcirculation. Clarifying the mechanism of microcirculating damage is obviously a key step to understand the pathogenesis of ABMR. Here we characterized capillary variation in ABMR and its possible mechanisms. Compared with T cell-mediated rejection and stable grafts, there was a significant dilation and rarefaction in peritubular capillaries (PTCs) of the ABMR group; Image-Pro Plus revealed a significantly larger intra-PTC area. Interestingly, the dilation of PTCs was strongly correlated with the intra-PTC cell counting. Moreover, peritubular capillary inflammation is correlated with in situ T-bet expression, and there was a good correlation between the intra-PTC expression of T-bet and the PTC diameter. HIF-1α up-regulation could be observed in ABMR but it was not necessary for capillary dilation. In general, ABMR is characterized with early capillary dilation and rarefaction; our data confirmed that the dilation is strongly correlated with intracapillary inflammation, which in turn is correlated with in situ T-bet expression. T-bet plays an important role in the development of microcirculating injury, and thus it is a potential target for the treatment of ABMR.

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Figures

Figure 1
Figure 1
Peritubular capillary (PTC) dilation and rarefaction in antibody-mediated rejection (ABMR). Labeling the endothelial cells for CD31 showed PTC dilation and rarefaction in ABMR group (a), compared with PTC staining in T cell-mediated rejection (TCMR) group (b). (c) PTC density among the three groups revealed a rarefaction of PTCs in ABMR group. (d) PTC diameters among the three groups revealed significant PTC dilation in ABMR group. (e) Intra-PTC areas among the three groups revealed significant PTC enlargement in ABMR group. (a, b) Original magnification, ×400.
Figure 2
Figure 2
The relationship between microcirculation inflammation and peritubular capillary (PTC) dilation. In the antibody-mediated rejection group, PTC diameter (a) and intra-PTC area (b) were strongly correlated with the number of intra-PTC cells.
Figure 3
Figure 3
T-bet expression in antibody-mediated rejection (ABMR). (a) Quantitative measurement of the number of intra-PTC T-bet-expressing cells in the ABMR, T cell-mediated rejection (TCMR), and stable graft (SG) groups. In the ABMR group, T-bet expression was strongly correlated with the quantity of infiltrating cells (b) and peritubular capillary (PTC) diameter (c).
Figure 4
Figure 4
HIF-1α expression in antibody-mediated rejection (ABMR) and T cell-mediated rejection (TCMR). Double staining of CD31 and HIF-1α showed capillary dilation, and HIF-1α expression occurred somewhat in parallel both in ABMR (a) and TCMR (b) while HIF-1α expression was not necessary for capillary dilation. Original magnification, ×400.
Figure 5
Figure 5
Capillary variation between antibody-mediated rejection (ABMR) and transplant glomerulopathy (TG). CD31 and CD68 (labeled in brown) costaining showed peritubular capillary (PTC) dilation was much more severe in the TG group (a) than in the ABMR group (b).

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