Gf. Schreiner et al., MODULATION OF THE KINETICS OF THE INITIAL LEUKOCYTE MIGRATION INTO RENAL-ALLOGRAFTS BY 16,16-DIMETHYL PGE2, Transplantation, 56(2), 1993, pp. 417-422
Host sensitization to vascular allografts is induced by the interactio
n between host lymphocytes, antigen-presenting cells, and the allograf
t. However, little is known concerning the nature or kinetics of the i
nitial host leukocyte migration into the transplanted organ prior to i
mmune sensitization. Employing a model of donor-irradiated renal allog
rafts and isografts, we have characterized the participating cell type
s and the kinetics of the leukocyte influx during the first 96 hr afte
r engraftment. Both isografts and allografts experience a marked initi
al influx of host leukocytes into the renal interstitium, peaking at 4
8 hr after transplantation. Concomitant glomerular accumulation of leu
kocytes is much less marked. By 96 hr, the leukocyte influx into isogr
afts has significantly diminished, while allografts demonstrate a subs
equent 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 th
e monocyte/macrophage, with a smaller component of T lymphocytes. Neut
rophils and B lymphocytes are not found in this initial infiltrate. In
tragraft infusion of dimethyl PGE2 markedly inhibits the monocyte infl
ux 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 interstiti
um of isografts. The results suggest that one mechanism by which PGE m
ay inhibit host sensitization to allografts may be suppression of the
initial influx of donor monocytes into the newly allografted organ.