Differential patterns of circulating intercellular adhesion molecule-1 (cICAM-1) and vascular cell adhesion molecule-1 (cVCAM-1) during liver allograft rejection.

During allograft rejection, adhesion molecules play an integral role in infiltration, activation, and binding of effector cells to target tissue. Some adhesion molecules, including ICAM-1 and VCAM-1, exist in soluble, circulating forms that retain ligand-binding activity. In the present study the levels of circulating ICAM-1 (cICAM-1) and VCAM-1 (cVCAM-1) were compared in the serum and bile of pediatric liver recipients. The cICAM-1 was significantly elevated in the serum during allograft rejection and infection relative to periods when no rejection was apparent. Biliary cICAM-1, however, was specifically elevated during rejection and not during infection or when no rejection was apparent. The cVCAM-1 levels were elevated in the serum during rejection compared with levels when no rejection was evident. In contrast, cVCAM-1 was not detected in the bile. Serum levels of both cICAM-1 and cVCAM-1 decreased rapidly following successful treatment for rejection, whereas elevated levels persisted, or increased, in ongoing rejection. The differential patterns of the circulating forms of ICAM-1 and cVCAM-1 were consistent with the membrane expression of these molecules during graft rejection. ICAM-1 expression was extensive on bile duct epithelium, endothelium, hepatocytes, and infiltrating leukocytes during rejection, while VCAM-1 was restricted to endothelium. These findings indicate that the release of circulating adhesion molecules is a prominent feature of liver allograft rejection. Measurement of these markers may be useful in distinguishing rejection from infection and in determining the efficacy of treatment for rejection.