Phagocytosis of dialysis-related amyloid deposits by macrophages

A 24-year-old man started haemodialysis in 1975. He had presented with proteinuria and microscopic haematuria in 1971, and developed severe hypertension and renal impairment in 1973. His kidneys were of a small size but no cysts were seen, despite a strong family history of autosomal dominant polycystic kidney disease. He had a subtotal parathyroidectomy for secondary hyperparathyroidism in 1982. He developed a typical dialysis-related amyloidosis with bilateral carpal tunnel syndrome, which was operated on in 1986 and 1988, as well as bilateral popliteal cysts limiting knee flexion, bilateral scapulohumeral periarthritis, and cervical spondyloarthropathy. In 1999 he underwent tenosynovectomy of the flexors and was operated on again for right carpal tunnel syndrome. Small blocks (approximately 1 mm) of the tissue obtained surgically from his right carpal tunnel were fixed in 4% (wuv) paraformaldehyde and 0.1% (vuv) glutaraldehyde in PBS. Ultrathin sections (60–90 nm) were immuno-labelled with anti-b2-microglobulin (Nordic, Tilburg, The Netherlands) and anti-amyloid P component (APC) (Dako, Glostrup, Denmark) antibodies. Specific immuno-labelling was assessed with 10 mm gold particles coupled with protein A, and observed with a Hitachi H-600 AB transmission electron microscopy (Hitachi, Tokyo, Japan). Figure 1 shows an electron micrograph of a macrophage in contact with fibrillar material (an amyloid) mainly in the extracellular space (EC). Amyloid material was labelled with both the antibodies used. Labelling was much more dense with anti-b2-microglobulin antibodies (Figure 1A, C and D) than with anti-APC antibodies (Figure 1B), confirming that, although APC is present, it occurs far less commonly in amyloid fibrils than b2-microglobulin does. It can be seen that the cell developed protrusions to surround the amyloid fibrils. The figure shows different stages of encircling the amyloid material: the protrusion (thin arrows) grows from (A) to (B) and bilaterally encompasses the labelled fibrils in (C). Figure 1(D) shows the incorporated gold-labelled amyloid fibrils in the intracellular space in a patchy distribution (wide arrows) along with the remaining EC amyloid material diffusely labelled.