PMID- 7533347 OWN - NLM STAT- MEDLINE DCOM- 19950406 LR - 20171116 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 59 IP - 4 DP - 1995 Feb 27 TI - Upregulation of cytokines associated with macrophage activation in the Lewis-to-F344 rat transplantation model of chronic cardiac rejection. PG - 572-8 AB - 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 upregulated in hearts undergoing chronic rejection. Gene transcript levels for IFN-gamma, monocyte chemoattractant protein-1 (MCP-1), and IL-6 were measured with reverse-transcription PCR assays optimized for each gene. Gene products were confirmed by immunohistology. 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-gamma 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 interstitium and vasculature. The sustained expression of these cytokines in cardiac allografts undergoing chronic rejection supports the widely held hypothesis that the intimal changes associated with transplant arteriosclerosis are mediated by cellular activation and cytokine production. FAU - Russell, M E AU - Russell ME AD - Harvard School of Public Health, Boston, Massachusetts. FAU - Wallace, A F AU - Wallace AF FAU - Hancock, W W AU - Hancock WW FAU - Sayegh, M H AU - Sayegh MH FAU - Adams, D H AU - Adams DH FAU - Sibinga, N E AU - Sibinga NE FAU - Wyner, L R AU - Wyner LR FAU - Karnovsky, M J AU - Karnovsky MJ LA - eng GR - HL43318/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (CD4 Antigens) RN - 0 (CD8 Antigens) RN - 0 (Chemotactic Factors) RN - 0 (DNA, Complementary) RN - 0 (Interleukin-6) RN - 0 (Monocyte Chemoattractant Proteins) RN - 63231-63-0 (RNA) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Base Sequence MH - CD4 Antigens/analysis MH - CD8 Antigens/analysis MH - Chemotactic Factors/*analysis MH - DNA, Complementary MH - Graft Rejection/*immunology MH - *Heart Transplantation MH - Interferon-gamma/*analysis MH - Interleukin-6/*analysis MH - Macrophage Activation MH - Molecular Sequence Data MH - Monocyte Chemoattractant Proteins MH - Myocardium/immunology MH - RNA/analysis MH - Rats MH - Rats, Inbred F344 MH - Rats, Inbred Lew MH - Transplantation, Homologous EDAT- 1995/02/27 00:00 MHDA- 1995/02/27 00:01 CRDT- 1995/02/27 00:00 PHST- 1995/02/27 00:00 [pubmed] PHST- 1995/02/27 00:01 [medline] PHST- 1995/02/27 00:00 [entrez] PST - ppublish SO - Transplantation. 1995 Feb 27;59(4):572-8.