Kidney allograft transplantation improved the prognosis and quality of life of patients with end-stage renal diseases but the occurrence of acute rejection represents a limitation of the final outcome. Noninvasive biomarkers are needed as well as further advancements in the understanding of immune mechanisms of reaction to the allograft. Our study of 138 patients focused on one-year monitoring of serum concentrations of 12 chemokines regulating the recruitment of different immune cells into transplanted allograft and on in vitro regulation of the same chemokines release by interactions of renal proximal epithelial cells with monocyte/macrophage cell line stimulated with TNF alpha. In a group of 44 patients with acute rejection, higher serum pretransplant levels of CXCL1, CXCL5, CXCL6, CCL2, CCL21, and particularly CXCL10 and CX3CL1(both p < 0.001) were found suggesting their higher proinflammatory status as compared to subjects with the uncomplicated outcome. In samples collected at the day of biopsy positive for acute rejection, chemokines CXCL9 and CXCL11 attracting preferentially Th1 lymphocytes were found to be upregulated. In our in vitro model with TNF alpha induction, renal proximal epithelial cells seemed to be a more potent source of chemokines attracting neutrophils as compared to monocyte/macrophage cell line but the coculture of these cells potentiated release of neutrophilic chemokines CXCL5 and CXCL6. Similar augmentation of chemokine production was found also in the case of CCL2. On the other hand, adding of monocytes/macrophages to a culture of renal epithelial cells suppressed the release of CXCL10 and CXCL11 attracting T lymphocytes. We assume from our data that in kidney allograft transplantation, chemokines attracting neutrophils, T lymphocytes, and monocytes are induced simultaneously and measurement some of them in combination might be used as biomarkers of acute rejection. Mutual cell-cell interactions of immune cells with renal parenchyma seem to be important for fine regulation of chemokine release.
- MeSH
- alografty MeSH
- chemokin CCL2 krev MeSH
- chemokin CCL21 krev MeSH
- chemokin CX3CL1 krev MeSH
- chemokin CXCL1 krev MeSH
- chemokin CXCL10 krev MeSH
- chemokin CXCL11 krev MeSH
- chemokin CXCL5 krev MeSH
- chemokin CXCL6 krev MeSH
- chemokin CXCL9 krev MeSH
- chemokiny krev MeSH
- kvalita života MeSH
- lidé MeSH
- rejekce štěpu krev imunologie MeSH
- Th1 buňky metabolismus MeSH
- transplantace ledvin škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Tumour progression requires the presence of a rich vascular supply. A number of cytokines, chemokines and proteases participate in the process of tumour angiogenesis. We evaluated serum levels of angiogenin, panGRO (Growth Related Oncogene) (CXCL 1,2,3) and ENA-78 (Epithelial Neutrophil Activating) (CXCL5) in the serum of 32 patients with RCC (renal cell carcinoma) and 14 healthy blood donors by means of a protein array analysis. The patients were divided into three groups according to their disease stages (I+II, III, IV). We discovered significant differences between the blood donors and patients with RCC both in pre-operative and post-operative angiogenin, panGRO and ENA-78 levels. The increase in angiogenic factors lasted in patients even without metastases 2 months after surgery. We found no correlation between the levels of angiogenin and stages I+II, III and IV RCC. Patients with advanced carcinoma (stage III) had pre-operatively higher serum levels of ENA-78 than patients with stages I+II (p = 0,009) and IV (p< 0.001). Eight weeks after surgery the patients with stages I+II had significantly higher levels of panGRO than patients with stage IV.
- MeSH
- chemokin CXCL1 krev MeSH
- chemokin CXCL5 krev MeSH
- dospělí MeSH
- karcinom z renálních buněk chirurgie krev patologie MeSH
- látky indukující angiogenezi krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin chirurgie krev patologie MeSH
- pankreatická ribonukleasa krev MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
