Assessment of the charge-selectivity of glomerular basement
membrane using ficoll sulfate.
Bolton, Glen R., William M. Deen, and Barbara S. Daniels.
Department of Chemical Engineering, Massachusetts Institute of
Technology, Cambridge, MA 02139, and Department of Medicine,
University of Minnesota, Minneapolis, MN 55455
APStracts 5:0023F, 1998.
The extent to which the glomerular basement membrane (GBM) contributes
to the charge- selectivity of the glomerular capillary wall has been
controversial. To reexamine this issue, the size- and charge
-selectivity of filters made from isolated rat GBM were assessed using
polydisperse ficoll and ficoll sulfate as test macromolecules. Ficoll
sulfate, a novel tracer with spherical shape synthesized for this
purpose, exhibited little or no binding to serum albumin, thereby
avoiding a major difficulty that has been reported with dextran
sulfate. The sieving coefficients of ficoll sulfate were not
different from those of ficoll at physiological ionic strength,
although the values for ficoll sulfate were depressed at low ionic
strength. These results confirm that the GBM possesses fixed negative
charges, but suggest that its charge density is insufficient to
confer significant charge-selectivity under physiological conditions,
where electrostatic interactions are relatively well screened. The
sieving coefficients of ficoll sulfate and ficoll were elevated
significantly, and by similar amounts, when bovine serum albumin
(BSA) was present in the retentate at 4 g/dl. This could be explained
as the combined effect of two non-specific physical factors, namely,
the reduction in filtration velocity due to the osmotic pressure of
BSA, and the effect on macromolecular partitioning of repulsive
solute-solute interactions. The view that BSA does not affect the
intrinsic properties of the GBM is supported also by the absence of
an effect on the hydraulic permeability of isolated GBM. The sieving
coefficient of BSA was roughly half that of ficoll or ficoll sulfate
of similar Stokes-Einstein radius. Given the finding of negligible
charge- selectivity, this difference may be attributed to the
nonspherical shape of albumin. The results suggest that, to the
extent that isolated GBM is similar to GBM in vivo, the charge
-selectivity of the glomerular capillary wall must be due to the
endothelial and/or epithelial cell layers.
Received 18 September 1997; accepted in final form 16 January
1998.
APS Manuscript Number F299-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 28 January 1998