Immunohistochemical localization of apolipoprotein A-IV in human kidney tissue.
BACKGROUND
Apolipoprotein A-IV (ApoA-IV) is a 46 kD glycoprotein thought to protect against atherosclerosis. It is synthesized primarily in epithelial cells of the small intestine. Elevated plasma concentrations of ApoA-IV in patients with chronic kidney disease suggest that the human kidney is involved in ApoA-IV metabolism.


METHODS
To investigate whether the human kidney directly metabolizes ApoA-IV and which kidney tissue compartment is involved therein, ApoA-IV was localized by immunohistochemistry in 28 healthy kidney tissue samples obtained from patients undergoing nephrectomy. ApoA-IV mRNA expression was analyzed by real-time polymerase chain reaction (PCR) to exclude de novo synthesis in the kidney.


RESULTS
ApoA-IV immunostaining was detected in proximal and distal tubular cells, capillaries and blood vessels but not inside glomeruli. ApoA-IV was predominantly found in the brush border of proximal tubules and in intracellular granules and various plasma membrane domains of both proximal and distal tubules. mRNA expression analysis revealed that no ApoA-IV was produced in the kidney.


CONCLUSIONS
The immunoreactivity of ApoA-IV observed in kidney tubular cells suggests a direct role of the human kidney in ApoA-IV metabolism. The granular staining pattern probably represents lysosomes degrading ApoA-IV. The additional ApoA-IV localization in distal tubules suggests a rescue function to reabsorb otherwise escaping ApoA-IV in case proximal tubules cannot reabsorb all ApoA-IV. Since no mRNA expression could be detected in any kidney cells, the observed ApoA-IV immunoreactivity represents uptake and not de novo synthesis of ApoA-IV.
Haiman
Marina
M
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
Salvenmoser
Willi
W
Scheiber
Karl
K
Lingenhel
Arno
A
Rudolph
Christian
C
Schmitz
Gerd
G
Kronenberg
Florian
F
Dieplinger
Hans
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D001054:Apolipoproteins A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D008113:Liver Neoplasms; D008297:Male; D008875:Middle Aged
D001054:Apolipoproteins A; C022205:apolipoprotein A-IV