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Mouse Models of Renal Allograft Transplant Rejection: Methods to Investigate Chemokine–GAG Interaction and Therapeutic Blockade

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Abstract

Chemokine–glycosaminoglycan (GAG) interactions direct immune cell activation and invasion, e.g., directing immune cells to sites of infection or injury, and are central to initiating immune responses. Acute innate and also adaptive or antibody-mediated immune cell responses both drive damage to kidney transplants. These immune responses are central to allograft rejection and transplant failure. While treatment for acute rejection has advanced greatly, ongoing or chronic immune damage from inflammation and antibody-mediated rejection remains a significant problem, leading to transplant loss. There are limited numbers of organs available for transplant, and preventing chronic graft damage will allow for longer graft stability and function, reducing the need for repeat transplantation. Chemokine–GAG interactions are the basis for initial immune responses, forming directional gradients that allow immune cells to traverse the vascular endothelium and enter engrafted organs. Targeting chemokine–GAG interactions thus has the potential to reduce immune damage to transplanted kidneys. Mouse models for renal transplant are available, but are complex and require extensive microsurgery expertise. Here we describe simplified subcapsular and subcutaneous renal allograft transplant models, for rapid assessment of the roles of chemokine–GAG interactions during allograft surgery and rejection. These models are described, together with treatment using a unique chemokine modulating protein (CMP) M-T7 that disrupts chemokine–GAG interactions.

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