ALLOANTIGEN-DEPENDENT ENDOTHELIAL PHENOTYPE AND LYMPHOKINE MESSENGER-RNA EXPRESSION IN REJECTING MURINE CARDIAC ALLOGRAFTS

Recent studies suggest that graft microvascular endothelia may play an important role in the regulation of rejection. Alloantigen-dependent changes in microvascular endothelial phenotype may be associated with differences in infiltrate function in allografts vs. isografts, as ref lected in alloantigen-specific CTL accumulation and cytokine productio n. To correlate cytokine production with differences in microvascular endothelial phenotype during allograft inflammation, we used PCR to id entify cytokine mRNAs isolated from pooled cardiac isografts and allog rafts on days 1, 3, and 5 after transplantation. Graft microvascular e ndothelia express an inflamed phenotype associated with wound healing and the repair of tissue damage due to mechanical trauma, ischemia, an d/or reperfusion injury-i.e., high levels of ICAM-1 expression and MEC A-32 mAb reactivity. By day 1 in both isografts and allografts, mRNAs for the cytokines IL1alpha, IL6, TNF, LT, and TGFbeta are upregulated or induced. By the third day in cardiac allografts, an antigen-depende nt endothelial phenotype is expressed, characterized by the presence o f cell surface VCAM-1. Concomitantly, mRNAs for the lymphokines IL2 an d IFNgamma are detected, followed by IL4 mRNA by day 5. The expression of VCAM-1 by allograft endothelia may influence the inflammatory proc ess, by physically recruiting specific T cell subpopulations into the response and/or by delivering additional signals to the infiltrating c ells. Eventually, these and other regulatory events occurring at these early times initiate a process that later results in alloreactive tis sue destruction.