Analysis of Macrophage Phenotype in Rejected Corneal Allografts

Oh, Joo Youn; Lee, Hyun Ju; Ko, Ah Young; Ko, Jung Hwa; Kim, Mee Kum; Wee, Won Ryang

doi:10.1167/iovs.13-12650

Cited by 26 publications

(32 citation statements)

References 27 publications

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“…Notably, M1 macrophages are inflammatory cells, whereas M2 macrophage resolve inflammation and thus play critical roles in tissue remodeling and wound healing. Previous reports of corneal studies indicate that M2 macrophages function in the wound repair process in this tissue [21,26]. Therefore, our observation that H 2 treatment promotes M2 macrophage expression suggests another potential clinical application of this therapy.…”

Section: Discussionsupporting

confidence: 60%

Hydrogen promotes the activation of Cu, Zn superoxide dismutase 1 in a rat corneal alkali-burn model

Arima

Igarashi

Uchiyama

et al. 2019

Preprint

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Background Although interest in the field of hydrogen (H2) medicine is growing, few reports have described the effects of H2 in the activation of Cu, Zn superoxide dismutase (SOD) 1 in an ophthalmological context. This study aimed to investigate the effects of H2 on SOD1 activation in a rat model of corneal alkali burn. Methods In each rat, one cornea was subjected to alkali exposure. Physiological saline (saline group) or H2-dissolved saline (H2 group) was instilled continuously on the cornea for 5 minutes before and after alkali exposure. Inflammatory cells, neovascularization, and cytoplasmic SOD1 levels were evaluated immunohistochemically in enucleated eyes from both groups. Additionally, three-dimensional ultrastructural tissue changes in the eyes were analyzed using low-vacuum scanning electron microscopy. Results The numbers of both inflammatory and vascular endothelial cells were significantly reduced in the corneas of the H2 group. Furthermore, H2 treatment increased both cytoplasmic SOD1 levels and activity in corneal epithelial cells. Notably, the SOD1 activity level in the H2 group was approximately 2.5-fold greater than that in the saline group. Conclusions H2 treatment suppressed inflammation and neovascularization in the injured cornea and indirectly suppressed oxidative insult to the cornea by upregulating the SOD1 enzyme protein level and activity.

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Section: Discussionsupporting

confidence: 60%

Hydrogen promotes the activation of Cu, Zn superoxide dismutase 1 in a rat corneal alkali-burn model

Arima

Igarashi

Uchiyama

et al. 2019

Preprint

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“…While M1 macrophages mediate injury, M2 macrophages are generally implicated in injury resolution and tissue remodeling, and therefore, they may promote allograft damage repair; though currently, their role in acute injury remains speculative. Histological studies of murine corneal allografts exhibiting acute rejection revealed the presence of M1 macrophages secreting proinflammatory mediators, while M2 macrophages were detected in the animals that did not reject the transplants [64]. An M1-dominant response was also observed in a rat model of acute renal AMR and in clinical biopsy samples of acutely rejecting kidney allograft recipients [65].…”

Section: Macrophages In Acute Allograft Rejectionmentioning

confidence: 99%

The divergent roles of macrophages in solid organ transplantation

Salehi

Reed

2015

Current Opinion in Organ Transplantation

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Purpose of review This review summarizes the phenotype and function of macrophages in the context of solid organ transplantation and will focus on fundamental insights into their paradoxical pro-inflammatory versus suppressive function. We will also discuss the therapeutic potential of regulatory macrophages in tolerance induction. Recent findings Macrophages are emerging as an essential element of solid organ transplantation. Macrophages are involved in the pathogenesis of ischemia reperfusion injury, as well as both acute and chronic rejection, exacerbating injury through secretion of inflammatory effectors and by amplifying adaptive immune responses. Notably, not all responses associated with macrophages are deleterious to the graft, and graft protection can in fact be conferred by macrophages. This has been attributed to the presence of macrophages with tissue-repair capabilities, as well as the effects of regulatory macrophages. Summary The explosion of new information on the role of macrophages in solid organ transplantation has opened up new avenues of research and the possibility of therapeutic intervention. However, the role of myeloid cells in graft rejection, resolution of rejection and tissue repair remains poorly understood. A better understanding of plasticity and regulation of monocyte polarization is vital for the development of new therapies for the treatment of acute and chronic transplant rejection.

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“…Although mechanisms and molecules associated with macrophage plasticity and polarized activation have been studied in tumors, diseases of the central nervous system, or tissue transplantation (Biswas and Mantovani 2010; Oh et al 2013; Sica 2010; Shechter and Schwartz 2013), there have been few studies on differentiation and distribution of macrophages in dry eye associated inflammation. Thus, we investigated the phenotype of macrophages in ocular surface tissues of experimental dry eye in mice.…”

Section: Introductionmentioning

confidence: 99%

Macrophage Phenotype in the Ocular Surface of Experimental Murine Dry Eye Disease

You

Coursey

Bian

et al. 2015

Arch. Immunol. Ther. Exp.

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To evaluate the phenotype of macrophages in the cornea and conjunctiva of C57BL/6 mice with induced experimental dry eye. C57BL/6 mice exposed to desiccating stress (DS) were evaluated at 1, 5, and 10 days and C57BL/6 mice maintained in non-stressed environment were used as controls. Whole eyes and adnexa were excised for histology or used for gene expression analysis. Location and phenotype of macrophages infiltrating the cornea and conjunctiva was evaluated by immunofluorescence analysis. Quantitative polymerase chain reaction evaluated macrophage markers and T cell-related and inflammatory cytokine expression in cornea and conjunctiva. Immunofluorescence staining demonstrated that macrophages reside in the conjunctiva of control and dry eye mice and their number did not change with DS. Real-time RT-PCR demonstrated that the level of M1 macrophage marker, iNOS, increased prominently in the conjunctiva at DS 10 days. In contrast, there was a non-significant decrease of the M2 marker Arg1 with DS. The levels of inflammatory cytokine, IL-12a mRNA transcript in the conjunctiva increased significantly at DS1 and decreased at DS5, while levels of IL-18 were significantly increased at DS 10. Macrophages reside in the ocular surface tissues of C57BL/6 mice. Although the number of macrophages in the conjunctiva does not change, evidence of inflammatory M1 activation after desiccating stress was observed. Better understanding of phagocyte diversity and activation in dry eye disease provide a basis for the development of phagocyte-targeted therapeutic strategies.

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Analysis of Macrophage Phenotype in Rejected Corneal Allografts

Abstract: Increased numbers of macrophages in rejected corneal allografts implicate that these cells might contribute to the immunopathogenesis of corneal graft rejection.

Cited by 26 publications

References 27 publications

Hydrogen promotes the activation of Cu, Zn superoxide dismutase 1 in a rat corneal alkali-burn model

Hydrogen promotes the activation of Cu, Zn superoxide dismutase 1 in a rat corneal alkali-burn model

The divergent roles of macrophages in solid organ transplantation

Macrophage Phenotype in the Ocular Surface of Experimental Murine Dry Eye Disease

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