Kojiro Nakamura1,2,3, Shoichi Kageyama1, Jerzy W Kupiec-Weglinski1. 1. Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, California, USA. 2. Department of Surgery, Kyoto University, Kyoto. 3. Department of Surgery, Nishi-Kobe Medical Center, Kobe, Hyogo, Japan.
Abstract
PURPOSE OF REVIEW: Although organ transplantation has become the standard life-saving strategy for patients with end-stage organ failure and those with malignancies, effective and safe therapeutic strategies to combat allograft loss remain to be established. With the emerging evidence suggesting the critical role of innate immunity in the mechanism of allograft injury, we summarize the latest understanding of macrophage-neutrophil cross-communication and discuss therapeutic prospects of their targeting in transplant recipients. RECENT FINDINGS: Macrophages and neutrophils contribute to the pathogenesis of early peritransplant ischemia-reperfusion injury and subsequent allograft rejection immune cascade, primarily by exacerbating inflammatory response and tissue damage. Noteworthy, recent advances enabled to elucidate multifaceted functions of innate immune cells, which are not only deleterious but may also prove graft-protective. Indeed, the efficacy of macrophage polarizing regimens or macrophage-targeted migration have been recognized to create graft-protective local environment. Moreover, novel molecular mechanisms in the neutrophil function have been identified, such as neutrophil extracellular traps, tissue-repairing capability, crosstalk with macrophages and T cells as well as reverse migration into the circulation. SUMMARY: As efficient strategies to manage allograft rejection and improve transplant outcomes are lacking, newly discovered, and therapeutically attractive innate immune cell functions warrant comprehensive preclinical and clinical attention.
PURPOSE OF REVIEW: Although organ transplantation has become the standard life-saving strategy for patients with end-stage organ failure and those with malignancies, effective and safe therapeutic strategies to combat allograft loss remain to be established. With the emerging evidence suggesting the critical role of innate immunity in the mechanism of allograft injury, we summarize the latest understanding of macrophage-neutrophil cross-communication and discuss therapeutic prospects of their targeting in transplant recipients. RECENT FINDINGS: Macrophages and neutrophils contribute to the pathogenesis of early peritransplant ischemia-reperfusion injury and subsequent allograft rejection immune cascade, primarily by exacerbating inflammatory response and tissue damage. Noteworthy, recent advances enabled to elucidate multifaceted functions of innate immune cells, which are not only deleterious but may also prove graft-protective. Indeed, the efficacy of macrophage polarizing regimens or macrophage-targeted migration have been recognized to create graft-protective local environment. Moreover, novel molecular mechanisms in the neutrophil function have been identified, such as neutrophil extracellular traps, tissue-repairing capability, crosstalk with macrophages and T cells as well as reverse migration into the circulation. SUMMARY: As efficient strategies to manage allograft rejection and improve transplant outcomes are lacking, newly discovered, and therapeutically attractive innate immune cell functions warrant comprehensive preclinical and clinical attention.
Authors: Francine M Almeida; Angela S Battochio; João P Napoli; Katiusa A Alves; Grace S Balbin; Manoel Oliveira-Junior; Henrique T Moriya; Paulo M Pego-Fernandes; Rodolfo P Vieira; Rogerio Pazetti Journal: Nutrients Date: 2020-09-10 Impact factor: 5.717