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Journal of Histochemistry and Cytochemistry, Vol. 47, 313-322, March 1999, Copyright © 1999, The Histochemical Society, Inc.

ARTICLE

Localization and Characterization of Antithrombin in Human Kidneys

Ronald J. Torrya, Carlos A. Labarrerea, David Nelsonb, Antonio Pantaleoc, and W. Page Faulka
a Division of Experimental Pathology, Methodist Research Institute, Clarian Health (Methodist, IU, Riley Hospitals), Indianapolis, Indiana
b Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio
c Department of Endocrinology, University of Rome, La Sapienza, Rome, Italy

Correspondence to: Ronald J. Torry, College of Pharmacy and Health Sciences, Drake Univ., 2507 University Ave., Des Moines, IA 50311. Fax: (515) 271-1867.

Antithrombin is a serine protease inhibitor that is critical in maintaining a thromboresistant vasculature. The association between low serum antithrombin concentration and renal disease suggests that the kidney plays a role in the conservation of plasma antithrombin. We used immunohistochemical techniques to determine the spatial distribution, heparin binding characteristics, and intracellular and intercellular localization of antithrombin in biopsy specimens (n = 53) of human donor kidneys obtained at the time of transplantation. In the renal cortex, double antibody techniques demonstrated the presence of intracellular antithrombin in proximal tubule epithelial cells. The reactivity was granular and was co-localized with vesicle-like structures. Distal and collecting tubules did not demonstrate intraepithelial antithrombin reactivity. No tubule structures in the medullary region demonstrated intracellular antithrombin, but all these structures showed intense basement membrane antithrombin reactivity. Double antibody techniques also demonstrated that the heparin binding domain of intraepithelial antithrombin was occupied. Semiquantitative scores for intraepithelial antithrombin were significantly decreased in renal biopsy specimens obtained 30 min after anastomosis compared with biopsies from the same organ obtained before anastomosis. These findings suggest that antithrombin, probably in association with heparin or heparan sulfate, is internalized by renal proximal epithelial cells. Although the ultimate fate of intraepithelial antithrombin is not known, this may represent a mechanism by which the kidney helps to maintain plasma antithrombin concentrations. (J Histochem Cytochem 47:313–321, 1999)

Key Words: tubule epithelium, proximal tubules, microvasculature, transplantation, renal cortex, renal medulla


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