Phenotype of Rat Monocytes During Acute Kidney Allograft Rejection: Increased Expression of NKR-P1 and Reduction of CD43

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Abstract

Monocytes and macrophages mediate cytotoxicity after appropriate activation and thus represent effectors secondary to T lymphocytes and natural killer (NK) cells. However, very little is known about the role of activated monocytes in organ allograft rejection. In this study, isogeneic(LEW to LEW) and fully allogeneic (DA to LEW) rat kidneys were grafted to bilaterally nephrectomized recipients. Four days after transplantation a comprehensive sample of leucocytes was recovered by perfusion of the recipients' vasculature with phosphate-buffered saline containing EDTA(PBS/EDTA). Monocytes were enriched by density gradient centrifugation and their physical parameters and immunophenotype were investigated by flow cytometry in comparison with untreated, specified pathogen-free (SPF) LEW rats. Isotransplantation and allotransplantation of kidneys dramatically increased the absolute number of intravascular monocytes in the recipient. Analysis of NKR-P1 (CD161), CD4, CD62L, CD43, CD11a, CD18 and MHC class II expression identified at least two monocyte populations in all experimental groups. In graft recipients it was evident that activated monocytes were able to express and upregulate NKR-P1 and CD8, which have not been detected in these cells to date. If activated monocytes utilize NKR-P1 and CD8, by analogy to NK cells and lymphocytes these cells may be endowed with additional pathways to upregulate cytolytic functions and effect allograft damage.

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