Fractalkine is Crucial in Ischemia Reperfusion Injury Related to Acute Rejection in an Allogeneic Heart Transplantation Model

T. Kanzawa¹, D. Tokita¹, T. Yamakawa¹, H. Ishigooka¹, H. Fukuda¹, H. Katsumata¹, S. Miyairi¹, R. Ishii¹, T. Hirai¹, K. Saiga¹, M. Okumi¹, T. Imai², K. Tanabe¹

¹Urology, Tokyo Women's Medical University, Tokyo, Japan, ²KAN Research Institute, Kobe, Japan

Meeting: 2019 American Transplant Congress

Abstract number: B8

Keywords: Ischemia, Mice, Rejection

Session Information

Session Name: Poster Session B: Ischemia Reperfusion & Organ Rehabilition

Session Type: Poster Session

Date: Sunday, June 2, 2019

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: Ischemia reperfusion injury (IRI) facilitates allograft rejection in renal transplantation recipients (IRI-related rejection). Controlling IRI improves graft survival. Fractalkine (FKN) is an inflammatory chemokine. FKN expression by vascular endothelial cells is induced by IRI. Its receptor, CX3CR1, is expressed on different kinds of immune cells. The interaction of FKN with CX3CR1 allows migration of CX3CR1-positive immune cells into damaged or inflammatory tissues. We hypothesized that FKN-CX3CR1 interaction is crucial in IRI-related allograft rejection, and examined whether anti-FKN antibody could block FKN-CX3CR1 interaction and prevent IRI-related rejection in a murine heterotopic heart transplantation model.

*Methods: Wild type (WT) C57BL/6 mice received heterotopic heart transplants from BALB/c mice. CTLA4-immunoglobulin was administered (0.25 mg) on days 0 and 1, and anti-FKN antibody on days -1, 3, 7, 10, and 14. We transplanted donor hearts preserved at 4°C for 8 hours (IRI group) or 0.5 hours (control group) into CX3CR1 knock-out C57BL/6 mice. Graft rejection was diagnosed by stopping pulsation. FKN expression in cardiac allografts was analyzed by immunohistochemistry.

*Results: FKN was expressed on vascular endothelial cells in cardiac allografts from the IRI group on day 3. Graft survival rates were significantly lower than control group rates (P = 0.0303, log-lank test). To clarify the importance of CX3CR1 in IRI-related rejection, donor hearts preserved at 4°C for 8 hours were transplanted in CX3CR1 knock-out mice. Graft survival in these mice was significantly higher than in WT recipients (P = 0.0226). Anti-FKN antibody blockade of FKN-CX3CR1 interaction prolonged graft survival in mice transplanted with donor hearts preserved at 4°C for 8 hours (P = 0.0178, vs untreated mice).

*Conclusions: FKN-CX3CR1 interaction is crucial in IRI-related rejection in allogeneic transplantation. Anti-FKN antibody has a potential to improve the outcome of deceased-donor transplantation by blocking FKN-CX3CR1 interaction.

To cite this abstract in AMA style:

Kanzawa T, Tokita D, Yamakawa T, Ishigooka H, Fukuda H, Katsumata H, Miyairi S, Ishii R, Hirai T, Saiga K, Okumi M, Imai T, Tanabe K. Fractalkine is Crucial in Ischemia Reperfusion Injury Related to Acute Rejection in an Allogeneic Heart Transplantation Model [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/fractalkine-is-crucial-in-ischemia-reperfusion-injury-related-to-acute-rejection-in-an-allogeneic-heart-transplantation-model/. Accessed May 11, 2025.

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