Cardiac Allograft Rejection in the Absence of Macrophage Migration Inhibitory Factor

Demir, Yilmaz; Chen, Yifa; Metz, Christine N.; Renz, Harald; Heeger, Peter S.

doi:10.1097/01.tp.0000067241.06918.24

Cited by 13 publications

(10 citation statements)

References 11 publications

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“…Grafts were considered fully rejected when they were Ͼ90% necrotic. Vascularized heterotopic cardiac grafts obtained from 8-to 10-wk-old donors were placed in the abdomen as described and palpated daily for evidence of a heartbeat (4,8,29). For selected experiments, donor hearts were obtained from 3-wk-old donors.…”

Section: Placement and Evaluation Of Skin And Cardiac Graftsmentioning

confidence: 99%

“…Formalin-fixed paraffin sections of graft tissues were stained with H&E and for elastin as described elsewhere (4,8,29). Vasculopathy was quantified by calculating the neointimal index (NI) as described by Armstrong et al (30,31) and by reporting the number of vessels with Ͼ30% vasculopathy per graft.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…The number and activation state of graft-derived dendritic cells capable of priming recipient T cells (13,14), the presence of ischemia-reperfusion injury to the graft (15,16), and the number of foreign Ags expressed by the graft (11,17) are among the donor characteristics that may contribute to the immunogenicity of a transplanted organ. Once the recipient T cells are activated, potentially relevant factors that determine whether these lymphocytes will induce graft destruction include the quantity and distribution of Ag expressed on the individual graft cells (4,5,17,18), the subtype (CD4 vs CD8) of T cells activated in response to the transplant (19), the specific chemoattractant molecules that recruit T cells to graft site (2,3), the effector functions utilized by the activated T cells when they re-encounter their ligand at the graft site (cytokines produced, cytotoxicity) (4,8,9,17,18,20,21), and the frequency of effector T cells induced (11,17,22).…”

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confidence: 99%

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Effects of T Cell Frequency and Graft Size on Transplant Outcome in Mice

Schenk

Zhang

et al. 2004

The Journal of Immunology

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The features that determine whether graft-reactive T lymphocytes develop into effector cells capable of mediating organ destruction are not well understood. To investigate potential factors involved in this process, we first confirmed that female recipient mice acutely rejected minor Ag-disparate male skin, but not heart transplants. Despite this difference in outcome, heart and skin transplantation induced antidonor T cell responses of similar magnitude, specificity, and cytokine profile. The heart-graft-primed T cells transiently infiltrated the graft and ultimately induced the development of chronic transplant vasculopathy. Increasing the frequency of donor-reactive T cells by presensitization or by using TCR (CD8+ antimale)-transgenic recipients did not mediate acute rejection but accelerated the pace and severity of the vasculopathy. Surprisingly, decreasing the tissue mass of the donor heart by 50% resulted in acute rejection of these smaller grafts without increasing the frequency of antidonor effector T cells in the recipients. In complementary studies, placement of one or two male skin grafts on a single recipient did not affect the frequency or cytokine profile of the induced antimale T cell repertoire. Nonetheless, the recipients of single grafts acutely rejected the transplanted skin while the recipients of two skin grafts did not. These results provide new insight into the pathogenesis of transplant vasculopathy and provide an explanation for the difference in outcome between murine skin and heart transplants by highlighting the novel concept that the efficiency of transplant-reactive T cell immunity is heavily influenced by the tissue burden it encounters at the effector stage.

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Section: Placement and Evaluation Of Skin And Cardiac Graftsmentioning

confidence: 99%

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of T Cell Frequency and Graft Size on Transplant Outcome in Mice

Schenk

Zhang

et al. 2004

The Journal of Immunology

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“…MIF production is upregulated in cases of kidney or heart graft rejection, as demonstrated by animal and human studies [87][88][89]. Neutralising anti-MIF antibodies can inhibit indirect allorecognition of skin grafts, probably partly through inhibition of macrophages [41].…”

Section: Mif and Islet Transplantationmentioning

confidence: 99%

“…Blockade of MIF production with a liposome-transfected small interfering RNA prevented early obstructive bronchiolitis and destruction in a mouse tracheal allograft model [90]. Conversely, murine cardiac and renal allograft rejections were not prevented or even delayed in MIF KO recipients or by use of anti-MIF neutralising antibodies [42,89].…”

Section: Mif and Islet Transplantationmentioning

confidence: 99%

The role of macrophage migration inhibitory factor on glucose metabolism and diabetes

et al. 2008

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Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in many inflammatory reactions and disorders, and it has become evident that it also affects glucose homeostasis. The protein is produced by pancreatic beta cells and can promote the release of insulin. It also modulates glucose uptake, glycolysis and insulin resistance in insulin target cells such as the adipocyte, myocyte and cardiomyocyte. Possessing both immunological and endocrinological properties, MIF has been associated with the development of type 1 and type 2 diabetes, and it may be important in the setting of islet transplantation. The present review summarises our current knowledge, based on clinical and research data, on the impact of MIF on both physiological and pathological aspects of glucose metabolism.

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Macrophage-migration inhibitory factor: role in inflammatory diseases and graft rejection

Javeed

Zhao²

2008

Inflamm. res.

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Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein, participating in inflammatory and immune responses. MIF was originally discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including production of proinflammatory cytokines, glucocorticoid-induced immunomodulator, and natural killer cell inhibitory factor (NKIF), regulation of toll-like receptor expression, adherence and phagocytosis of macrophages, as well as induction of metalloproteinase. Therefore MIF is considered as a potential target protein in many pathophysiological states. In this review, considering the protein structure and the acting mechanisms of MIF, we mainly discuss the important role of MIF in pathogenesis of inflammatory diseases and graft rejection.

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Cardiac Allograft Rejection in the Absence of Macrophage Migration Inhibitory Factor

Abstract: MIF is not required for acute or chronic allograft rejection in mice. The findings raise questions about the role of DTH as an important mediator of cardiac allograft injury.

Cited by 13 publications

References 11 publications

Effects of T Cell Frequency and Graft Size on Transplant Outcome in Mice

Effects of T Cell Frequency and Graft Size on Transplant Outcome in Mice

The role of macrophage migration inhibitory factor on glucose metabolism and diabetes

Macrophage-migration inhibitory factor: role in inflammatory diseases and graft rejection

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