BACKGROUND: Graft rejection after liver transplantation is associated with a lymphocytic infiltrate, the nature of which will be determined by, among various factors, the local activity of chemokines that attract particular subsets of effector cells to the graft. METHODS: The expression of chemokines and receptors in @entity1 liver allografts was studied by immunohistochemistry of tissue and flow cytometry of blood and liver-derived lymphocytes. Receptor function was assessed with in vitro chemotaxis. RESULTS: We report increased expression of chemokine receptors @entity366 , @entity436 , and @entity5075 on circulating and graft-infiltrating lymphocytes after liver transplantation. Liver-derived T cells responded to the ligands for these receptors in vitro, which suggests that the receptors are functionally active. The chemokine ligands for these receptors were detected in rejecting allografts. @entity366 ligands interferon-inducible protein 10 and monokine-induced by gamma interferon were detected on sinusoidal endothelium and @entity372 was detected on portal and hepatic vascular endothelium, whereas the @entity436 ligand, stromal-derived factor (SDF), was restricted to biliary epithelium. @entity5075 ligands have previously been shown on portal endothelium. An in vitro model of T-cell alloactivation demonstrated a similar pattern of expression of functional @entity366 , @entity436 , and @entity5075 on T cells. Increased expression of chemokine receptors, especially @entity23427 and @entity5075 , was associated with redistribution of activated Kupffer cells in rejecting grafts. CONCLUSIONS: The patterns of chemokine expression in liver allografts during rejection suggest that the recruitment and positioning of lymphocytes is mediated by specific chemokines. Although ligands for the receptors @entity366 and @entity5075 are important for recruitment, the restriction of SDF to bile ducts suggests that @entity436 may be involved in the retention of alloactivated lymphocytes at sites of graft damage.

Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting XXXX liver transplants.

@entity1 :: ('9606', 'Species') :: ['human'] @entity23427 :: ('1232', 'Gene') :: ['CCR3'] @entity5075 :: ('1234', 'Gene') :: ['CCR5'] @entity366 :: ('2833', 'Gene') :: ['CXCR3'] @entity372 :: ('6373', 'Gene') :: ['interferon-inducible T-cell alpha chemoattractant'] @entity436 :: ('7852', 'Gene') :: ['CXCR4']
@entity1 :: (9606,Species) :: ['human']
