Altered localization of protamine-heparin complexes in aminonucleoside nephrosis
Seiler, M.W.; Hoyer, J.R.; Krueger, T.E.
Laboratory Investigation; a Journal of Technical Methods and Pathology 43(1): 9-17
1980
ISSN/ISBN: 0023-6837 PMID: 6993788 Document Number: 155134
Spherical protamine-heparin complexes (PH complexes) are formed in situ during sequential perfusion of rat kidneys with protamine and heparin. The effects of aminonucleoside nephrosis on the ultrastructural and immunofluorescent localization of PH complexes was studied in proteinuric rats 8-10 days after i.v. injection or unilateral renal perfusion with the aminonucleoside of puromycin. In normal control kidneys PH complexes were most numerous in the lamina rara externa of the glomerular basement membrane; the largest complexes were present in filtration slits. The PH complexes in areas of glomerular basement membrane overlying the mesangium were markedly fewer and smaller than in the periphery. In nephrotic kidneys the pattern of PH complex localization was markedly altered. Complexes in the peripheral capillary walls beneath the extensive areas of epithelial cell foot process fusion were greatly reduced; the number of PH complexes in the mesangial and paramesangial regions of these diseased kidneys were greatly increased. The PH complexes in the remaining filtration slits were larger than normal. The alterations in PH complex localization in nephrotic kidneys were much greater than the changes in glomerular basement membrane anionic sites demonstrated after perfusion with protamine alone. The mechanism of the increase in size and number of PH complexes in mesangial regions and in filtration slits may involve altered glomerular hydrodynamics and increased hydraulic flow through these regions in the nephrotic glomeruli. The increased mesangial uptake of macromolecules in aminonucleoside nephrosis shown in earlier studies could also be a consequence of such changes in glomerular hydrodynamics. [The localization of protamine-heparin complexes in aminonucleoside nephrosis was used as a model to demonstrate the importance of glomerular properties in determining the sites of immune complex localization within the glomeruli in immunologically mediated human renal diseases.].