Identification and upregulation of galactose/N-acetylgalactosamine macrophage lectin in rat cardiac allografts with arteriosclerosis.
Using differential mRNA display to uncover potential mediators associated with chronic rejection, we identified a cDNA fragment induced in Lewis to F344 rat cardiac allografts with arteriosclerosis but not Lewis syngrafts. The full-length cDNA (1.4 kb) isolated from a rat cardiac allograft cDNA library was 99% identical to galactose/N-acetylgalactosamine (Gal/GalNAc) macrophage lectin, a cell-surface receptor. This cDNA hybridized in Northern analysis with total RNA from eight cardiac allografts but not with host hearts, syngrafts, or other organs. There was a significant allograft-specific increase in transcript levels measured by reverse transcriptase PCR at days 7, 14, 28, and 75 in comparison with paired F344 host hearts (subject to same circulation but histologically normal), day-0 hearts, and syngrafts (P < 0.008, n = 4 at each time). Transcript levels in cardiac allografts were higher than those in paired host spleens (a major source of inflammatory cells) (P < 0.0001), indicating the localized nature of Gal/GalNAc lectin induction. By in situ hybridization and immunostaining, Gal/GalNAc lectin expression localized to a subset of inflammatory cells in cardiac allografts. These findings link Gal/GalNAc macrophage lectin to the chronic rejection process, as a possible mediator of macrophage infiltration.
Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115.
M E
ME
Russell
U
U
Utans
A F
AF
Wallace
P
P
Liang
R J
RJ
Arceci
M J
MJ
Karnovsky
L R
LR
Wyner
Y
Y
Yamashita
C
C
Tarn
D000116:Acetylgalactosamine / Q000235:genetics*; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D001483:Base Sequence; D005690:Galactose / Q000235:genetics*; D005786:Gene Expression Regulation; D016027:Heart Transplantation; D037102:Lectins / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D037102:Lectins; D012333:RNA, Messenger; D000116:Acetylgalactosamine; D005690:Galactose