In vivo antibody-mediated modulation of aminopeptidase A in mouse proximaltubular epithelial cells

Citation
S. Mentzel et al., In vivo antibody-mediated modulation of aminopeptidase A in mouse proximaltubular epithelial cells, J HIST CYTO, 47(7), 1999, pp. 871-880
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
ISSN journal
0022-1554 → ACNP
Volume
47
Issue
7
Year of publication
1999
Pages
871 - 880
Database
ISI
SICI code
0022-1554(199907)47:7<871:IVAMOA>2.0.ZU;2-I
Abstract
Aminopeptidase A (APA) is one of the many renal hydrolases. In mouse kidney , APA is predominantly expressed on the brush borders and sparsely on the b asolateral membranes of proximal tubular epithelial cells. However, when la rge amounts of monoclonal antibodies (MAbs) against APA were injected into mice, we observed strong binding of the MAbs to the basolateral membranes, whereas the MAbs bound only transiently to the brush borders of the proxima l tubular epithelial cells. In parallel, APA itself disappeared from the br ush borders by both endocytosis and shedding, whereas it was increasingly e xpressed on the basolateral sides. Using ultrastructural immunohistology, w e found no evidence for transcellular transport of endocytosed APA to the b asolateral side of the proximal tubular epithelial cells. The absence of tr anscellular transport was confirmed by experiments in which we used a low d ose of the MAbs. Such a low dose did not result in binding of the MAbs to t he brush borders and had no effect on the presence of APA in the brush bord ers of the proximal tubular epithelial cells. in these experiments we still could observe binding of the MAbs to the basolateral membranes in parallel with the local appearance of APA. In addition, treatment of mice with chlo rpromazine, a calmodulin antagonist that interferes with cytoskeletal funct ion, largely inhibited the MAb-induced modulation of APA. Our studies sugge st that injection of MAbs to APA specifically interrupts the normal intrace llular traffic of this enzyme in proximal tubular epithelial cells. This in tracellular transport is dependent on the action of cytoskeletal proteins.