Evidence that increases in lymphocyte tyrosine phosphorylation precede cardiac allograft rejection: Effects of cyclosporine and potential use in clinical management

Peter W. Tsao, Gordon B. Mills, Roberto J. Diaz, Ingeborg C. Radde, Diane Parkinson, Jill Waddell, Greg J. Wilson, John G. Coles

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Tyrosine phosphorylation is an early, critical event in lymphocyte signal transduction. We measured tyrosine phosphorylation in a porcine experimental transplant model to evaluate its utility in monitoring the allograft immune response. Using flow cytometry, we demonstrate a biphasic increase in phosphoty-rosine (ptyr) levels in peripheral blood mononuclear cells (PBMC), and that increases are detectable as early as 1 day posttransplantation in untreated transplanted animals (n=4). This biphasic response is likely result from the sequestration of ptyr+ cells from the periphery into the graft as graft-infiltrating lymphocytic cells show increased ptyr levels. This suggests possible lymphocyte trafficking between the peripheral compartment and the allograft. A 5-day course of treatment with cyclosporine (CsA) at 20 mg/kg/day (n=4), but not at 10 mg/kg/day (n=4), prevents graft rejection in this allograft model. Strikingly, treatment with 20 mg/kg/day CsA, but not with 10 mg/kg/day, suppressed increases in ptyr levels in both PBMC and graft-infiltrating cells. Increases in ptyr levels in PBMC are detectable 2-5 days before histologic and electrocardiographic signs of graft rejection, suggesting a potential diagnostic utility for measuring tyrosine phosphorylation in monitoring and managing transplant rejection.

Original languageEnglish (US)
Pages (from-to)451-457
Number of pages7
JournalTransplantation
Volume58
Issue number4
DOIs
StatePublished - Aug 27 1994
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'Evidence that increases in lymphocyte tyrosine phosphorylation precede cardiac allograft rejection: Effects of cyclosporine and potential use in clinical management'. Together they form a unique fingerprint.

  • Cite this