Up-regulation of macrophage migration inhibitory factor in acute renal allograft rejection in the rat

Fiona G. Brown, D. J. Nikolic-Paterson, C. Metz, R. Bucala, R. C. Atkins, H. Y. Lan

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

Abstract

Recent studies have identified a key role for macrophage migration inhibitory factor (MIF) in a number of immune cell-mediated diseases. The current study investigated the potential role of MIF in acute allograft rejection. Lewis rats underwent bilateral nephrectomy and then received an orthotopic DA renal allograft or an orthotopic Lewis renal isograft. Groups of six animals were killed at day 1 or 5 after transplantation. No immunosuppression was used. Animals receiving a renal allograft exhibited severe rejection on day 5, as shown by high levels of serum creatinine, very low rates of creatinine clearance, and severe tubulitis with a dense macrophage and T cell infiltrate. In contrast, isografts had normal renal function on day 5 with no histological evidence of rejection. Northern blotting showed that renal MIF mRNA expression was unchanged at day 1, but was increased 3.5-fold on day 5. In situ hybridization showed a marked increase in MIF mRNA expression by tubular cells and MIF mRNA expression by many infiltrating mononuclear cells in day 5 allografts. Immunostaining confirmed an increase in tubular MIF protein expression, particularly in areas of severe tubular damage with prominent leucocytic infiltration. Double staining showed that many infiltrating macrophages and T cells expressed the MIF protein in day 5 allografts. There was only a minor increase in MIF expression in day 5 isografts, demonstrating that neither surgical injury nor stress cause significant up-regulation of MIF expression in allograft rejection. In conclusion, this study has demonstrated that local MIF production is specifically increased in acute renal allograft rejection. These results suggest that MIF may play an important role in the cellular immune response mediating acute allograft rejection.

Original languageEnglish
Pages (from-to)329-336
Number of pages8
JournalClinical and Experimental Immunology
Volume118
Issue number2
DOIs
Publication statusPublished - 17 Nov 1999

Keywords

  • Immunohistochemistry
  • Macrophage
  • Macrophage migration inhibitory factor
  • T cell
  • Transplantation

Cite this

@article{54791fbd1ddd410aa502e69550cabee3,
title = "Up-regulation of macrophage migration inhibitory factor in acute renal allograft rejection in the rat",
abstract = "Recent studies have identified a key role for macrophage migration inhibitory factor (MIF) in a number of immune cell-mediated diseases. The current study investigated the potential role of MIF in acute allograft rejection. Lewis rats underwent bilateral nephrectomy and then received an orthotopic DA renal allograft or an orthotopic Lewis renal isograft. Groups of six animals were killed at day 1 or 5 after transplantation. No immunosuppression was used. Animals receiving a renal allograft exhibited severe rejection on day 5, as shown by high levels of serum creatinine, very low rates of creatinine clearance, and severe tubulitis with a dense macrophage and T cell infiltrate. In contrast, isografts had normal renal function on day 5 with no histological evidence of rejection. Northern blotting showed that renal MIF mRNA expression was unchanged at day 1, but was increased 3.5-fold on day 5. In situ hybridization showed a marked increase in MIF mRNA expression by tubular cells and MIF mRNA expression by many infiltrating mononuclear cells in day 5 allografts. Immunostaining confirmed an increase in tubular MIF protein expression, particularly in areas of severe tubular damage with prominent leucocytic infiltration. Double staining showed that many infiltrating macrophages and T cells expressed the MIF protein in day 5 allografts. There was only a minor increase in MIF expression in day 5 isografts, demonstrating that neither surgical injury nor stress cause significant up-regulation of MIF expression in allograft rejection. In conclusion, this study has demonstrated that local MIF production is specifically increased in acute renal allograft rejection. These results suggest that MIF may play an important role in the cellular immune response mediating acute allograft rejection.",
keywords = "Immunohistochemistry, Macrophage, Macrophage migration inhibitory factor, T cell, Transplantation",
author = "Brown, {Fiona G.} and Nikolic-Paterson, {D. J.} and C. Metz and R. Bucala and Atkins, {R. C.} and Lan, {H. Y.}",
year = "1999",
month = "11",
day = "17",
doi = "10.1046/j.1365-2249.1999.01048.x",
language = "English",
volume = "118",
pages = "329--336",
journal = "Clinical and Experimental Immunology",
issn = "0009-9104",
publisher = "Blackwell Science Ltd Oxford BSL",
number = "2",

}

Up-regulation of macrophage migration inhibitory factor in acute renal allograft rejection in the rat. / Brown, Fiona G.; Nikolic-Paterson, D. J.; Metz, C.; Bucala, R.; Atkins, R. C.; Lan, H. Y.

In: Clinical and Experimental Immunology, Vol. 118, No. 2, 17.11.1999, p. 329-336.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Up-regulation of macrophage migration inhibitory factor in acute renal allograft rejection in the rat

AU - Brown, Fiona G.

AU - Nikolic-Paterson, D. J.

AU - Metz, C.

AU - Bucala, R.

AU - Atkins, R. C.

AU - Lan, H. Y.

PY - 1999/11/17

Y1 - 1999/11/17

N2 - Recent studies have identified a key role for macrophage migration inhibitory factor (MIF) in a number of immune cell-mediated diseases. The current study investigated the potential role of MIF in acute allograft rejection. Lewis rats underwent bilateral nephrectomy and then received an orthotopic DA renal allograft or an orthotopic Lewis renal isograft. Groups of six animals were killed at day 1 or 5 after transplantation. No immunosuppression was used. Animals receiving a renal allograft exhibited severe rejection on day 5, as shown by high levels of serum creatinine, very low rates of creatinine clearance, and severe tubulitis with a dense macrophage and T cell infiltrate. In contrast, isografts had normal renal function on day 5 with no histological evidence of rejection. Northern blotting showed that renal MIF mRNA expression was unchanged at day 1, but was increased 3.5-fold on day 5. In situ hybridization showed a marked increase in MIF mRNA expression by tubular cells and MIF mRNA expression by many infiltrating mononuclear cells in day 5 allografts. Immunostaining confirmed an increase in tubular MIF protein expression, particularly in areas of severe tubular damage with prominent leucocytic infiltration. Double staining showed that many infiltrating macrophages and T cells expressed the MIF protein in day 5 allografts. There was only a minor increase in MIF expression in day 5 isografts, demonstrating that neither surgical injury nor stress cause significant up-regulation of MIF expression in allograft rejection. In conclusion, this study has demonstrated that local MIF production is specifically increased in acute renal allograft rejection. These results suggest that MIF may play an important role in the cellular immune response mediating acute allograft rejection.

AB - Recent studies have identified a key role for macrophage migration inhibitory factor (MIF) in a number of immune cell-mediated diseases. The current study investigated the potential role of MIF in acute allograft rejection. Lewis rats underwent bilateral nephrectomy and then received an orthotopic DA renal allograft or an orthotopic Lewis renal isograft. Groups of six animals were killed at day 1 or 5 after transplantation. No immunosuppression was used. Animals receiving a renal allograft exhibited severe rejection on day 5, as shown by high levels of serum creatinine, very low rates of creatinine clearance, and severe tubulitis with a dense macrophage and T cell infiltrate. In contrast, isografts had normal renal function on day 5 with no histological evidence of rejection. Northern blotting showed that renal MIF mRNA expression was unchanged at day 1, but was increased 3.5-fold on day 5. In situ hybridization showed a marked increase in MIF mRNA expression by tubular cells and MIF mRNA expression by many infiltrating mononuclear cells in day 5 allografts. Immunostaining confirmed an increase in tubular MIF protein expression, particularly in areas of severe tubular damage with prominent leucocytic infiltration. Double staining showed that many infiltrating macrophages and T cells expressed the MIF protein in day 5 allografts. There was only a minor increase in MIF expression in day 5 isografts, demonstrating that neither surgical injury nor stress cause significant up-regulation of MIF expression in allograft rejection. In conclusion, this study has demonstrated that local MIF production is specifically increased in acute renal allograft rejection. These results suggest that MIF may play an important role in the cellular immune response mediating acute allograft rejection.

KW - Immunohistochemistry

KW - Macrophage

KW - Macrophage migration inhibitory factor

KW - T cell

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=0011019505&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2249.1999.01048.x

DO - 10.1046/j.1365-2249.1999.01048.x

M3 - Article

VL - 118

SP - 329

EP - 336

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

SN - 0009-9104

IS - 2

ER -