Transport of Globin by the Renal Glomerulus

Abstract

Purified human globin injected into rats forms aggregates which are identifiable by their characteristic appearance in thin sections in the electron microscope and by their positive autoradiographs when the globin is tritiated before injection. Globin is taken up by endothelial cells of glomerular capillaries and is transported across the cell within the limits of a surrounding membrane. Globin is rarely seen to pass through fenestrations. Globin is also taken into the stalk region where it is seen usually within the sponge fibers and only occasionally within stalk cells. Globin is seen in all stages of passage through the basement membranes and sponge fibers, which are not deformed by its passage. On the basis of the findings presented here and by others, it is postulated that the basement membrane and sponge fibers consist of a thixotrophic gel. After traversing the basement membrane, the globin passes between foot processes of the epithelial cells. The slit membranes are deformed by this passage and thus appear to be distinctive structures. The globin is next found free in Bowman's space; the earliest aggregates are seen there within 1 minute after injection. Globin taken up in the stalk region is slowly discharged and very little is found there 6 hours postinjection.

Glomerular Permeability to Protein Molecules – its Possible Structural Basis

“…Other studies using electron opaque tracers, such as colloidal lanthanum [10,16,35,40] as well as elucidating the phagocytic function of mesangial cells [13,36,40,41], A gel like consistency of the GBM was inferred from studies using intravenously injected globin [40]. Sizable aggregates of globin traversed the GBM without visibly deforming the latter.…”

“…This suggested to M enefee el al. [40] that the GBM may behave like a thixotropic gel which liquefies under pressure. Although the so-called slit-pore membranes were deformed by the globin aggregates, they did not prevent the passage of globin into the urinary space.…”

“…To identify the structural equivalent of the glomerular permeability barrier, morphologists have relied on protein tracer molecules which can be visualized with the electron microscope [2,10,11,16,21,32,35,40,44,61], Although this approach has permitted certain structural-functional correlations to be made, the problem of defining the site of the filtration barrier in normal glomerular capillaries remains unresolved. The present review is restricted to those studies which have attempted to correlate ultrastructural-functional relationships of the glomerulus with its known permeability properties to proteins.…”

Fine Structural Basis for Hemoglobin Filtration by Glomerular Capillaries

“…The information obtained from these previous studies was limited by the fact that either abnormally large [D e o d h a r et al (4), F a rq u h a r and P alade (12,13), F a r q u h a r et al (14), F is h e r and H ellstrom (15), L atta et al (17)] or aggregated [M e n e f e e et al (18)] tracer molecules, or smaller but microscopically invisible compounds [F ish er and H ellstrom (15), V e r n ie r (28)] were used in the experiments. The filtration barrier for large mole cules, such as ferritin, colloidal gold, and thorotrast particles appeared to be located in the outer, pale portion of the basement membrane.…”

Role of Glomerular Basement Membrane Thixotropy and Influence of Glomerular Vascular Pressure in the Pathogenesis of Immune Complex-Induced Glomerulonephritis

“…What follows represents an updated version of the views expressed in 1975. Although my understanding of glom erular structure and function was extended through the writings of Zlabek [4], Menefee et al [5], Farquhar and Palade [6], Caulfield and Farquhar [7], Arakawa and Tokunaga [8], Rodewald and Karnowsky [9] and Skaaring and Kjaergaard [10] the greater part of my presently held views are based upon light, transmission and scanning electron microscopic studies of kidneys of female NZB x OUW Fi hybrid (BW) mice in our laboratory. The reproducibility of BW mouse disease, which has not changed its basic pattern in almost 20 years, has permitted the dynamics of ICGN to be studied in detail.…”