Expression of the fractalkine receptor (CX3CR1) in human kidney diseases

Background. CX3CL1 (fractalkine) is a membrane bound chemokine that can function as an adhesion molecule for cells expressing the receptor CX3CR1. This receptor is involved in the recruitment of inflammatory cells in a rat model of crescentic glomerulonephritis, where blockade of CX3CR1 has been shown to be of benefit. Here we describe the distribution of CX3CR1 positive cells in a variety of kidney diseases and renal development. Methods. A total of 84 formalin-fixed, paraffin-embedded specimens including fetal kidneys (N = 12), normal areas of kidneys uninvolved by neoplasia from tumor nephrectomies (N = 4), renal transplant nephrectomies (N = 5), renal transplant biopsies (N = 19), and kidney biopsies from patients with crescentic glomerulonephritis (N = 7), membranous nephropathy (N = 7), membranoproliferative glomerulonephritis (N = 8), focal and segmental glomerulosclerosis (N = 10), collapsing glomerulopathy (N = 6), and minimal change disease (N = 6) were studied. Immunohistochemistry was performed on consecutive tissue sections for CD3 positive T cells, CD68 positive monocyte/macrophages, CCR5 positive cells and CX3CR1 positive cells. Results. The majority of inflammatory leukocytes infiltrating the kidney expressed CX3CR1. The distribution pattern was consistent with expression by both T cells and monocytes/macrophages. In contrast to the distribution of CCR5, which was expressed on a subset of infiltrating cells predominantly localized in the interstitium, CX3CR1 was present on both interstitial and glomerular infiltrating leukocytes. In developing kidneys CX3CR1 positive cells formed a small, scattered population of cells, consistent with the distribution of infiltrating leukocytes. Conclusions. The high number of CX3CR1-positive inflammatory cells in various disease entities is consistent with its having a role in the accumulation of intrarenal inflammatory cells, but does not provide evidence of specificity of leukocytes bearing this receptor for specific types of injury. Other chemokine gradients, like those created by the ligands for the chemokine receptor CCR5, might subsequently guide leukocyte subsets to specific microenvironments.