Lambert C, Brealey R, Steele J, Rook G A
Department of Medical Microbiology, UCL Medical School, London, U.K.
Immunology. 1993 Jun;79(2):203-10.
Tamm-Horsfall protein (THP) is the major glycoprotein component of urine, yet its biological role remains obscure. Recent reports have suggested that a concanavalin A (Con A)-binding fraction of THP from pregnancy urine can bind the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). In order to investigate this claim in relation to THP from normal adult urine we raised monoclonal antibodies to THP and sought THP/TNF-alpha interactions in three separate assay systems. We found no evidence that THP binds to TNF-alpha under physiological conditions, but we observed that it exerts a weak, probably not physiologically relevant, but reproducible inhibitory effect on the toxicity of TNF-alpha for monolayers of L929 cells, even when the cells are pretreated with the THP, and washed before addition of the cytokine. Since our preparations of THP do not interact directly with TNF-alpha we postulated an interaction with the cells themselves, or with their extracellular matrix. The THP was found by ELISA, immunoblotting and immunohistology, to bind to as yet unidentified components of the extracellular matrix in a manner dependent on cations, pH and carbohydrates. These data, considered in the light of the published amino acid sequence and biochemical properties, suggest that THP is a member of a structural glycoprotein family known to modulate cell adhesion.
Tamm-Horsfall蛋白（THP）是尿液中的主要糖蛋白成分，但其生物学作用仍不清楚。最近的报告表明，来自妊娠尿液的THP的伴刀豆球蛋白A（Con A）结合部分可以结合细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）。为了研究与正常成人尿液中的THP相关的这一说法，我们制备了针对THP的单克隆抗体，并在三个独立的检测系统中寻找THP/TNF-α相互作用。我们没有发现证据表明THP在生理条件下与TNF-α结合，但我们观察到它对TNF-α对L929细胞单层的毒性有微弱的、可能与生理无关但可重复的抑制作用，即使细胞在用THP预处理并在添加细胞因子之前洗涤后也是如此。由于我们制备的THP不直接与TNF-α相互作用，我们推测它与细胞本身或其细胞外基质相互作用。通过酶联免疫吸附测定（ELISA）、免疫印迹和免疫组织学发现，THP以依赖于阳离子、pH和碳水化合物的方式与细胞外基质中尚未鉴定的成分结合。根据已发表的氨基酸序列和生化特性考虑这些数据，表明THP是已知调节细胞粘附的结构糖蛋白家族的成员。
