Sulfated HNK-1 Epitope in Developing and Mature Kidney: A New Marker for Thin Ascending Loop of Henle and Tubular Injury in Acute Tubular Necrosis

Abstract

The HNK-1 carbohydrate epitope is a 3-sulfo-glucuronyl residue attached to lactosamine structures on glycoproteins, proteoglycans, or glycolipids mostly expressed in the nervous system. Here, using monoclonal antibodies against the sulfated HNK-1 carbohydrate epitope, we first examined its distribution in developing and adult kidneys, then its expression in kidneys with tubular necrosis and renal neoplasms. This HNK-1 epitope was expressed in the human, rabbit, and rat, but not mouse kidney. It was detected within a subset of epithelial cells in the renal vesicle and in comma-and S-shaped bodies during early stages of nephrogenesis. In ureteral bud derivatives, the epitope was present transiently in the area where the collecting duct fused with the nephron. In the adult kidney, expression of the HNK-1 epitope became mainly restricted to the thin ascending loop of Henle where this epitope was carried by heparan-and chondro-proteoglycan. In pathological conditions, HNK-1 epitope expression increased dramatically in proximal epithelial tubule cells in kidneys with acute tubular necrosis. In tumors, the HNK-1 epitope was expressed in the epithelial component of nephroblastomas and in a subgroup of papillary renal cell carcinomas. These data suggest that molecules carrying the sulfated HNK-1 carbohydrate epitope may play an important role in critical stages of renal development and in the physiology of thin ascending loop of Henle. (J Histochem Cytochem 54:575-584, 2006)

Clinicopathological features and CD57 expression in renal cell carcinoma in acquired cystic disease of the kidneys: with special emphasis on a relation to the duration of haemodialysis, the degree of calcium oxalate deposition, histological type, and possible tumorigenesis

“…In the present study, CD57 (sulphated HNK-1 epitope), a marker of the ascending loop of Henle, 15 was expressed in neoplastic regions in many cases of ACDK-RCC, which suggests that many ACDK-RCCs have characteristics associated with the loop of Henle. Furthermore, the present finding that ACDK-RCCs frequently accompany oxalate crystals also correlates with the supposition that many of the epithelial cells of neoplastic regions have characteristics of the loop of Henle, from which nephrolithiasis including oxalate crystals may originate, and are included in these lesions.…”

“…Allory et al. 15 studied CD57 expression in conventional RCC (PRCC, 21/78, 26.9%; and CCC, 1/71, 1.4%), which bore little resemblance to those in the present 29 control cases of renal neoplasms without a history of haemodialysis, and was apparently lower than in the 29 RCCs in ACDK: not only in ACDK‐RCC (85.7%) but also in CCC (50.0%). These results suggest that not only many of the ACDK‐RCCs but also considerable numbers of CCCs in ACDK reveal stronger expression of Henle’s loop characteristics than conventional RCCs without ACDK, which may give rise to the histological diversity of ACDK‐RCC and difficulty in the classification of tumours according to the known subtypes of RCC.…”

“…Immunohistochemical studies were performed on representative paraffin‐embedded tissue blocks from all of the tumours using the labelled streptavidin–biotin method (Dako, Glostrup, Denmark). Five antibodies were used: cyclooxygenase‐2 (COX‐2), a marker of oxidative stress; Ki67 (MIB‐1), a marker of proliferative activity; CD57 (HNK‐1), a marker for the thin ascending loop of Henle; 15 CD10, a marker for the proximal tubule; and high‐molecular‐weight cytokeratin (CK‐HMW), a marker for the distal portion of the nephron. The sources of these primary antibodies and dilutions are summarized in Table 1.…”

Gain of Chromosomes 1, 2, 7, 10, 13 and 17 in an Acquired Cystic Kidney Disease Associated Renal Cell Carcinoma

“…We observed the oxalate deposition in both non-neoplastic cysts and tumor, consistent with previous observation [6]. We also found that both tumor and non-neoplastic cysts were positive for CD57, a marker of the ascending loop of Henle [8]. This observation suggests that oxalate deposition in both tumor and non-neoplastic cysts appear to be a result of expression of the Henle's loop characteristics [6].…”

Regulated expression and neural functions of human natural killer-1 (HNK-1) carbohydrate

“…In addition, HNK-1 expression in kidney seems to differ among species. In mouse, we found non-sulfated HNK-1 was expressed on apical membranes of proximal tubules and thin ascending limb in medulla, but in other species sulfated HNK-1 is expressed in thin ascending loop of Henle and may be carried by proteoglycan molecules [68]. So far, it is still unclear how the non-sulfated HNK-1 regulates the functions of these glycoproteins.…”