Introduction: Recent studies from our laboratory have documented a novel population of bone marrow derived granulocytes which are induced upon skin inflammation and are required to direct the subsequent infiltration of antigen-primed effector CD8+ T cells into the skin. These cells are Gr-1+, CXCR2+, CD11c+, B220- and express high levels of FasL and perforin. The goal of the current study is to investigate the role of this granulocyte subset in transplantation and ischemia-reperfusion injury (IRI).

Methods: A/J (H-2^a) or C57BL/6 (H-2^b) hearts were subjected to 0.5hrs or 4hrs of cold ischemia before being heterotopically transplanted to C57BL/6 WT or FasL/perforin-/- recipients. Renal IRI was conducted by 45mins of bilateral renal ischemia and assessment of serum creatinine 24hrs later. Gr-1+/CXCR2+ cells were purified from total bone marrow cells following transplantation and IRI by negative depletion of T, B, NK cells, and macrophages.

Results: Gr-1+/CXCR2+ granulocytes expressing FasL and perforin are observed within the bone marrow 4hrs following cardiac isograft or allograft transplantation despite being absent in the bone marrow of naÏve animals. Furthermore, these induced granulocytes were detectable within the graft tissue of transplanted animals at this early time point. As the duration of cold ischemia imposed on the cardiac graft was prolonged from 0.5 to 4hrs, generation of these FasL and perforin expressing granulocytes was significantly elevated in the recipient bone marrow. 24hrs after bilateral renal ischemic injury, serum creatinine in WT mice was significantly increased (1.1mg/dL) indicating severe renal dysfunction, whereas FasL/perforin-/- mice subjected to identical ischemic injury did not evidence increased serum creatinine (0.22mg/dL). These data suggest an important role for these early infiltrating granulocytes in mediating tissue injury and organ dysfunction following reperfusion of ischemic donor organs.

Conclusion: These data demonstrate the rapid generation of granulocytes expressing FasL and perforin within the bone marrow of mice following IRI. These novel granulocytes infiltrate transplanted grafts and organs subjected to ischemic insult early on and significantly contribute to IRI associated organ injury.

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