Ww. Hancock et al., LEW-TO-F344 CAROTID-ARTERY ALLOGRAFTS - ANALYSIS OF A RAT MODEL OF POSTTRANSPLANT VASCULAR INJURY INVOLVING CELL-MEDIATED AND HUMORAL RESPONSES, Transplantation, 60(12), 1995, pp. 1565-1572
A key manifestation of chronic rejection is an obliterative arterioscl
erosis, Myointimal thickening in the vessel is preceded by an endothel
ialitis involving accumulation of host mononuclear cells in the periva
scular and intimal spaces, We report a paratopic LEW-to-F344 rat carot
id artery transplantation model developed to study the cells, cytokine
s, and inflammatory response associated with this early phase of vascu
lar immune injury, Compared with contralateral control arteries and is
ografts, LEW-to-F344 carotid allografts develop intimal thickening wit
h mononuclear cell infiltration that persists (days 20, 45, 75, 90, an
d 120). Allografted vessels had dense collections of intimal and adven
titial leukocytes (CD45+) consisting of equal numbers of T cells and m
acrophages, There were small but variable numbers of intimal smooth mu
scle cells, Intimal cells showed dense staining for tumor necrosis fac
tor-alpha, interleukin-8, platelet-derived growth factor, iNOS, and IC
AM and weaker labeling for interleukin-1 beta and interleukin-6, There
was also prominent staining for interleukin-4 and interleukin-7 with
no detectable interferon-gamma or interleukin-alpha staining and high
titer labeling for IgG1 (but not IgG2). The predominance of the T cell
infiltrate coupled with interleukin-4 and IgG1 expression in carotid
allografts is consistent with a TH2 response. This contrasts with ball
oon-injured rat carotids, which evoke a macrophage-dependent prolifera
tive response, These findings demonstrate that there are distinct as w
ell as common activation pathways in various forms of vascular injury
and the LEW-to-F344 carotid model provides the opportunity to gain ins
ight into molecular mechanisms regulating alloimmune injury in the ves
sel.