Upregulation of cytokines associated with macrophage activation in the lewis-to-F344 rat transplantation model of chronic cardiac rejection

Mary E. Russell, Africa F. Wallace, Wayne W. Hancock, Mohamed H. Sayegh, David H. Adams, Nicholas E.S. Sibinga, Lauri R. Wyner, Morris J. Karnovsky

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Lewis-to-F344 rat cardiac allografts develop chronic rejection and arteriosclerotic lesions rich in mononuclear cells (especially macrophages). This study was performed to determine whether cytokine pathways associated with macrophage activation are upregu-lated in hearts undergoing chronic rejection. Gene transcript levels for IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IL-6 were measured with re-verse-transcription PCR assays optimized for each gene. Gene products were confirmed by immunohis-tology. For all three genes, transcript levels in rat cardiac allografts increased significantly on day 7 and remained elevated on days 14 and 28 posttransplantation, as compared with naive hearts, paired host hearts, and syngrafts (P<0.006). For the inducible genes IFN-γ and MCP-1, high transcript levels in cardiac allografts were in contrast with low levels in host spleens. On the other hand, transcript levels for the basally expressed gene IL-6 were elevated in both organs. Immunostaining confirmed allograft-specific expression for all three cytokines and localized the gene products to infiltrating mononuclear cells in the inter-stitium and vasculature. The sustained expression of these cytokines in cardiac allografts undergoing chronic rejection supports the widely held hypothesis that the intimai changes associated with transplant arteriosclerosis are mediated by cellular activation and cytokine production.

Original languageEnglish (US)
Pages (from-to)572-578
Number of pages7
JournalTransplantation
Volume59
Issue number4
StatePublished - Feb 27 1995
Externally publishedYes

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Macrophage Activation
Inbred F344 Rats
Up-Regulation
Transplantation
Cytokines
Allografts
Genes
Chemokine CCL2
Interleukin-6
Arteriosclerosis
Spleen
Macrophages
Transplants
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Russell, M. E., Wallace, A. F., Hancock, W. W., Sayegh, M. H., Adams, D. H., Sibinga, N. E. S., ... Karnovsky, M. J. (1995). Upregulation of cytokines associated with macrophage activation in the lewis-to-F344 rat transplantation model of chronic cardiac rejection. Transplantation, 59(4), 572-578.

Upregulation of cytokines associated with macrophage activation in the lewis-to-F344 rat transplantation model of chronic cardiac rejection. / Russell, Mary E.; Wallace, Africa F.; Hancock, Wayne W.; Sayegh, Mohamed H.; Adams, David H.; Sibinga, Nicholas E.S.; Wyner, Lauri R.; Karnovsky, Morris J.

In: Transplantation, Vol. 59, No. 4, 27.02.1995, p. 572-578.

Research output: Contribution to journalArticle

Russell, ME, Wallace, AF, Hancock, WW, Sayegh, MH, Adams, DH, Sibinga, NES, Wyner, LR & Karnovsky, MJ 1995, 'Upregulation of cytokines associated with macrophage activation in the lewis-to-F344 rat transplantation model of chronic cardiac rejection', Transplantation, vol. 59, no. 4, pp. 572-578.
Russell, Mary E. ; Wallace, Africa F. ; Hancock, Wayne W. ; Sayegh, Mohamed H. ; Adams, David H. ; Sibinga, Nicholas E.S. ; Wyner, Lauri R. ; Karnovsky, Morris J. / Upregulation of cytokines associated with macrophage activation in the lewis-to-F344 rat transplantation model of chronic cardiac rejection. In: Transplantation. 1995 ; Vol. 59, No. 4. pp. 572-578.
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