Macrophages as Effectors of Acute and Chronic Allograft Injury

Liu, Yianzhu; Kloc, Małgorzata; Li, Xian Chang

doi:10.1007/s40472-016-0130-9

Cited by 33 publications

(27 citation statements)

References 123 publications

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“…Insights such as these could be relevant to human disease. For example, it is conceivable that ASO therapeutics could be useful for treating rejection of cardiac allografts—a process in which macrophages are assumed to be effectors of tissue injury ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

High-resolution visualization and quantification of nucleic acid–based therapeutics in cells and tissues using Nanoscale secondary ion mass spectrometry (NanoSIMS)

Migawa

Chen

et al. 2020

Nucleic Acids Research

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Nucleic acid therapeutics (NATs) have proven useful in promoting the degradation of specific transcripts, modifying gene expression, and regulating mRNA splicing. In each situation, efficient delivery of nucleic acids to cells, tissues and intracellular compartments is crucial—both for optimizing efficacy and reducing side effects. Despite successes in NATs, our understanding of their cellular uptake and distribution in tissues is limited. Current methods have yielded insights into distribution of NATs within cells and tissues, but the sensitivity and resolution of these approaches are limited. Here, we show that nanoscale secondary ion mass spectrometry (NanoSIMS) imaging can be used to define the distribution of 5-bromo-2′-deoxythymidine (5-BrdT) modified antisense oligonucleotides (ASO) in cells and tissues with high sensitivity and spatial resolution. This approach makes it possible to define ASO uptake and distribution in different subcellular compartments and to quantify the impact of targeting ligands designed to promote ASO uptake by cells. Our studies showed that phosphorothioate ASOs are associated with filopodia and the inner nuclear membrane in cultured cells, and also revealed substantial cellular and subcellular heterogeneity of ASO uptake in mouse tissues. NanoSIMS imaging represents a significant advance in visualizing uptake and distribution of NATs; this approach will be useful in optimizing efficacy and delivery of NATs for treating human disease.

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Section: Discussionmentioning

confidence: 99%

High-resolution visualization and quantification of nucleic acid–based therapeutics in cells and tissues using Nanoscale secondary ion mass spectrometry (NanoSIMS)

Migawa

Chen

et al. 2020

Nucleic Acids Research

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“…Actually, emerging studies suggest that both adaptive immune cells and innate immune cells participate in transplant rejection [5–7]. Moreover, graft rejection in immunosuppressed patients emphasizes the key role of innate immune cells in graft rejection, including dendritic cells (DCs) [8], macrophages [9, 10], natural killer (NK) cells [11], and mast cells [12].…”

Section: Introductionmentioning

confidence: 99%

The Evolving Roles of Macrophages in Organ Transplantation

Cai

Zhuang

et al. 2019

Journal of Immunology Research

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Organ transplantation is a life-saving strategy for patients with end-stage organ failure. Over the past few decades, organ transplantation has achieved an excellent success in short-term survival but only a marginal improvement in long-term graft outcomes. The pathophysiology of graft loss is multifactorial and remains incompletely defined. However, emerging evidence suggests macrophages as crucial mediators of acute and chronic allograft immunopathology. In this process, macrophage-mediated mobilization of first-line defenses, particularly phagocytosis and the release of acute inflammatory mediators, is important, but macrophages also launch adaptive alloimmune reactions against grafts through antigen processing and presentation, as well as providing costimulation. Additionally, crosstalk with other immune cells and graft endothelial cells causes tissue damage or fibrosis in transplanted organs, contributing to graft loss or tolerance resistance. However, some macrophages function as regulatory cells that are capable of suppressing allogeneic T cells, inhibiting DC maturation, inducing the differentiation of Tregs, and subsequently promoting transplant tolerance. This functional diversity of macrophages in organ transplantation is consistent with their heterogeneity. Although our knowledge of the detrimental or beneficial effects of macrophages on transplants has exponentially increased, the exact mechanisms controlling macrophage functions are not yet completely understood. Here, we review recent advances in our understanding of the multifaceted nature of macrophages, focusing on their evolving roles in organ transplantation and the mechanisms involved in their activation and function in allograft transplantation. We also discuss potential therapeutic options and opportunities to target macrophage to improve the outcomes of transplant recipients.

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“…The progress in genetic matching nearly eliminated this type of rejection in clinical transplantation. In contemporary transplantation, the transplanted organs undergo two main types of rejection: acute rejection which occurs between the first week and 3 months post-transplantation, and chronic rejection which develops and progresses within many months or years post-transplantation [ 67 , 68 ]. Acute rejection is mainly driven by T cells, with some participation of macrophages, while chronic rejection mainly depends on the macrophages.…”

Section: Macrophage Response To Organ Transplantationmentioning

confidence: 99%

Macrophage Proinflammatory Responses to Microorganisms and Transplanted Organs

Kloc

Uosef

Kubiak

et al. 2020

IJMS

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Tissue-resident macrophages and those conscripted from the blood/bone marrow are professional phagocytes. They play a role in tissue homeostasis, replacement, and healing, and are the first-line responders to microbial (viral, bacterial, and fungi) infections. Intrinsic ameboid-type motility allows non-resident macrophages to move to the site of inflammation or injury, where, in response to the inflammatory milieu they perform the anti-microbial and/or tissue repair functions. Depending on the need and the signaling from the surrounding tissue and other immune cells, macrophages acquire morphologically and functionally different phenotypes, which allow them to play either pro-inflammatory or anti-inflammatory functions. As such, the macrophages are also the major players in the rejection of the transplanted organs making an excellent target for the novel anti-rejection therapies in clinical transplantation. In this review, we describe some of the less covered aspects of macrophage response to microbial infection and organ transplantation.

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Macrophages as Effectors of Acute and Chronic Allograft Injury

Cited by 33 publications

References 123 publications

High-resolution visualization and quantification of nucleic acid–based therapeutics in cells and tissues using Nanoscale secondary ion mass spectrometry (NanoSIMS)

High-resolution visualization and quantification of nucleic acid–based therapeutics in cells and tissues using Nanoscale secondary ion mass spectrometry (NanoSIMS)

The Evolving Roles of Macrophages in Organ Transplantation

Macrophage Proinflammatory Responses to Microorganisms and Transplanted Organs

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