Modulation of the kinetics of the initial leukocyte migration into renal allografts by 16,16-dimethyl PGE2.
Host sensitization to vascular allografts is induced by the interaction between host lymphocytes, antigen-presenting cells, and the allograft. However, little is known concerning the nature or kinetics of the initial host leukocyte migration into the transplanted organ prior to immune sensitization. Employing a model of donor-irradiated renal allografts and isografts, we have characterized the participating cell types and the kinetics of the leukocyte influx during the first 96 hr after engraftment. Both isografts and allografts experience a marked initial influx of host leukocytes into the renal interstitium, peaking at 48 hr after transplantation. Concomitant glomerular accumulation of leukocytes is much less marked. By 96 hr, the leukocyte influx into isografts has significantly diminished, while allografts demonstrate a subsequent additional rise in interstitial leukocytes coincident with the development of allosensitization. In allografts, the predominant cell type in the influx of the first 24-48 hr of the leukocyte influx is the monocyte/macrophage, with a smaller component of T lymphocytes. Neutrophils and B lymphocytes are not found in this initial infiltrate. Intragraft infusion of dimethyl PGE2 markedly inhibits the monocyte influx during the first 24-48 hr into the renal interstitium, but not the glomeruli, of allografts, while having relatively little effect on the migration of leukocytes into the renal glomerulus or renal interstitium of isografts. The results suggest that one mechanism by which PGE may inhibit host sensitization to allografts may be suppression of the initial influx of donor monocytes into the newly allografted organ.
Schreiner
G F
GF
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Kamei
T
T
Lefkowith
J
J
Flye
M W
MW
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D016030:Kidney Transplantation / Q000276:immunology*; D007700:Kinetics; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D015064:16,16-Dimethylprostaglandin E2