title: Organ-specific differences in the function of MCP-1 and CXCR3 during cardiac and skin allograft rejection.
abstract: BACKGROUND
  Chemokines are well-established to function in the recruitment of leukocytes into allografts in the course of rejection. Moreover, some studies have indicated that there are organ-specific differences in chemokine function, but the mechanism accounting for this difference is not known.
  
  
  METHODS
  Fully major histocompatibility complex-mismatched vascularized cardiac transplants or skin transplants were performed using BALB/c (H-2d), C57BL/6 (H-2b), MCP-1-/- (H-2b) and CXCR3-/- (H-2b) mice as donors or recipients. Also, skin grafts (H-2b) were placed onto SCID mice (H-2d) that received BALB/c splenocytes (H-2d) by adoptive transfer either at the time of transplantation, or after a period of 28 days.
  
  
  RESULTS
  Cardiac allografts in MCP-1-/- recipients survived significantly longer (P<0.0005) than wild-type (WT) controls. However, there was no prolongation of survival when MCP-1-/- grafts were used a donors in WT mice. In contrast, the absence of donor but not recipient MCP-1 prolonged skin allograft survival. WT donor cardiac grafts in CXCR3-/- recipients had a modest prolongation of survival (P<0.0005), whereas CXCR3-/- donor cardiac grafts in WT recipients were rejected similar to controls. Also, while recipient CXCR3 had no effect on the rejection of skin, CXCR3-/- donor skin grafts survived significantly longer than WT controls. This survival advantage was lost when vascularized CXCR3-/- skin grafts were used as donors in the SCID model of rejection.
  
  
  CONCLUSIONS
  Recipient derived MCP-1 and CXCR3 are functional in the rejection of vascularized, but not nonvascularized, allografts. In contrast, donor-derived MCP-1 and CXCR3 are functional in nonvascularized, but not vascularized grafts.
authors.affiliation: Transplantation Research Center and the Division of Nephrology, Children's Hospital Boston, and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Haskova
authors.forename: Atsushi
authors.initials: A
authors.lastname: Izawa
authors.forename: Alan G
authors.initials: AG
authors.lastname: Contreras
authors.forename: Evelyn
authors.initials: E
authors.lastname: Flynn
authors.forename: Gwenola
authors.initials: G
authors.lastname: Boulday
authors.forename: David M
authors.initials: DM
authors.lastname: Briscoe
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006084:Graft Rejection / Q000473:pathology*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine