Abstract: SA-PO985
Macrophage and T-Cell Infiltration in a Rat Model of Limb Ischemia: Effect of Impaired Kidney Function on the Pattern of Post-Ischemic Cell Infiltration
Session Information
- Hypertension and CVD: Mechanisms - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Hartner, Andrea, University Hospital of Erlangen, Erlangen, Germany
- Amann, Kerstin U., University Hospital Erlangen, Erlangen, Germany
- Veelken, Roland, University of Erlangen, Erlangen, Germany
- Hilgers, Karl F., University of Erlangen, Erlangen, Germany
Background
The outcome of limb ischemia is worse in rats with chronic kidney disease (CKD) as was previously shown by others and us. We hypothesized that a different pattern of T-lymphocyte and macrophage infiltration into the ischemic muscle in rats with CKD may underlie the deficient repair and angiogenesis processes.
Methods
CKD rats (N=10) underwent 5/6 nephrectomy; controls (N=8) sham operation. After 8 weeks, ischemia of the right limb was induced by ligation and resection of the femoral artery. Rats were sacrificed 3 days later. Cross sections of musculus soleus of the ischemic and non-ischemic limbs were stained for macrophage markers ED-1 and CD163 as well as lymphocyte markers CD3, CD4 and CD8a. Positive cells were counted in 20 high-power fields. The expression of a panel of cytokines (including CCL2, CCL5, CCL7, osteopontin, IL-6 and TNFα) in muscle tissue was measured by RT-PCR.
Results
All investigated cell types were increased in ischemic versus non-ischemic limbs. There was a trend towards a higher increase of ED-1 macrophages in ischemic limbs of CKD (15±3-fold versus 10±3-fold in controls, p=0.492) but there was no significant difference. Absolute numbers of ED-1 and CD163 positive cells as well as the ratio between ED-1 and CD163 (M2 macrophages) did not differ between CKD and control. The number of CD3 T-cells in ischemic limbs was not different between CKD (5.4±0.7 cells/view) and controls (4.9±0.5, p=0.897). However, the number of CD8a cells in ischemic limbs was higher in CKD (1.8±0.2) than in controls (1.0±0.1, p=0.006). The ratio of CD8a to CD4 cells was significantly elevated in CKD rat ischemic limbs, as was the ratio of CD8a to CD3 cells. All investigated cytokines increased in ischemic limbs but there was no consistent difference between CKD and controls. In ischemic limbs, CD8a cells correlated tightly with the expression of CCL5 (r=0.722, p=0.001) but not with other cytokines.
Conclusion
Our results point to a higher infiltration of CD8a cytotoxic T-cells into ischemic limbs in CKD rats which may contribute to a worse outcome. In contrast, we did not find an altered pattern of M1/M2 macrophages.
Funding
- Government Support - Non-U.S.