High Levels of Donor CCL2/MCP-1 Predict Graft-Related Complications and Poor Graft Survival After Kidney-Pancreas Transplantation

Abstract

In this study we analyzed the role of CCL2, a member of the chemokine family, in early graft damage. Using simultaneous kidney-pancreas transplantation (SPK) as a model, we showed that brain death significantly increases circulating CCL2 levels in humans. We found that in such situations, high donor CCL2 levels (measured before organ recovery and at the onset of cold preservation) correlate with increased postreperfusion release of CCL2 by both the graft and recipient throughout the week following transplantation (n = 28). In a retrospective study of 77 SPK recipients, we found a significant negative association between high donor levels of CCL2 and graft survival. Decreased survival in these patients is related to early posttransplant complications, including a higher incidence of pancreas thrombosis and delayed kidney function. Taken together our data indicate that high CCL2 levels in the donor serum predict both an increase in graft/recipient CCL2 production and poor graft survival. This suggests that the severity of the inflammatory response induced by brain death influences the posttransplant inflammatory response, independent of subsequent ischemia and reperfusion.

Role of CCL-2, CCR-2 and CCR-4 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury

“…Several receptors for chemokines such as CCR-1, CCR-2, CCR-4 and CCR-5 are detected in the same kind of diseases 5 11. Evidence accumulated that the ligands for CCR-1, CCR-2 and CCR-5 are ubiquitous in acute and chronic inflammatory lesions 21 22. This phenomenon has been characterised in experimental transplantation and inflammation of the central nervous system which elicit an inflammatory response, characterised by the expression of IL-8 and CCL-2 analogues 21 23 24.…”

Early Urinary CCL2 is Associated With the Later Development of Interstitial Fibrosis and Tubular Atrophy in Renal Allografts

“…Before organ recovery, an increased serum CCL2 level in deceased donors is associated with increased CCL2 release post-reperfusion from both the graft and recipient. Increased serum CCL2 in the recipients is associated with increased rates of delayed graft function and poor allograft survival (27). Urinary CCL2 is also increased in association with both subclinical and acute rejection episodes (16, 28 -30).…”

Dietary polyherbal supplementation decreases CD3+ cell infiltration into pancreatic islets and prevents hyperglycemia in nonobese diabetic mice

“…Synthesis and secretion of CCL2 are associated with poor function and survival of transplanted islets [61,62]. In addition, CXCL10 promotes recruitment of T-cells into islets [47] and also contributes to rejection of transplanted tissues [63].…”