Abstract: SA-PO461

Angiotensin-2 Expression Is Increased in Macrophages during Acute Cellular Rejection of Human Allografts

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Author

  • Zhang, Ping L., Beaumont Health System, Royal Oak, Michigan, United States
Background

The renin-angiotensin system (RAS) is well known to involve in hemodynamic changes in the kidney, but recent in vivo studies imply immunologic effects of RAS to cause damages in kidneys, partially through stimulating Interleukin-1 production by macrophages. We previously demonstrated that macrophages are one of dominantly cellular components in prominent acute cellular rejection (ACR). This study was to investigate whether there was an expression of angiotensin-2 (Ang2), the effector molecule in RAS, in macrophages involving ACR.

Methods

The study included 3 groups. The group 1, as the negative controls, was composed of 15 normal parenchyma sections away from renal cell carcinoma in nephrectomy specimens. The group 2, as the study group, consisted of 20 human allograft explant cases with ongoing ACR. As Ang2 is a small 8-peptid molecule being difficult for targeted staining, we selected 20 sarcoidosis cases (composed of aggregated and fused macrophages into giant cells), mostly known to have elevated serum angiotensin-converting enzymes, as the positive controls (4 in kidneys, and others in tonsil, liver and hilar lymph nodes). All paraffin embedded sections were stained for Ang2 by immunohistochemical staining method and cytoplasmic staining of Ang2 was graded 0 to 3+ (0 - no staining, 1+ - weak fine granular staining, 2+ - moderate granular staining and 3+ - strong granular staining).

Results

All negative controls (group 1) stained negatively for Ang2, as no or minimal inflammatory cells were present. All sarcoid granulomatous cells (macrophages and giant cells) in positive controls demonstrated moderate to prominent (2+ to 3+) positive staining for Ang2 in the cytoplasm. In macrophages involved in ACR of group 2, there was diffuse granular expression of Ang2 in macrophages with intensity ranging from 1+ to 3+. In the group 2, lymphocytes with scant cytoplasm appeared to stain weakly for Ang2 as well.

Conclusion

Using sarcoid granulomas as positive controls for Ang2 expression, the data indicate that Ang2 expression can be highly present in the activated macrophages involving in ACR of human allografts, implying Ang2 as a potential therapeutic target against ACR. In addition, the results from human specimens also support a notion that the RAS may affect some immunologic activities in the kidneys, based on previously in vitro and in vivo experiments.