The Passage of Protein Molecules Through the Glomerular Membranes

Bott, P. A.; Richards, A. N.

doi:10.1016/s0021-9258(18)72845-7

Cited by 37 publications

(4 citation statements)

References 30 publications

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“…Even though this barrier is not absolute, minimal amounts of protein normally leak into Bowman's space (7). Clearance of a particular macromolecule varies inversely with its size (1)(2)(3)(4)(5)(6), as evidenced by studies on the glomerular clearance of proteins and dextrans (5)(6)(7)(8)(9). In general, molecules smaller than tool wt 68,000 can pass into the urine, whereas those larger are effectively restricted.…”

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confidence: 99%

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An Ultrastructural Study of Glomerular Permeability Using Catalase and Peroxidase as Tracer Proteins

Venkatachalam

Karnovsky

Fahimi

et al. 1970

The Journal of Experimental Medicine

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The renal glomerulus effectively restricts plasma proteins and other macromolecules from entering the urinary space (1-6). Even though this barrier is not absolute, minimal amounts of protein normally leak into Bowman's space (7). Clearance of a particular macromolecule varies inversely with its size (1-6), as evidenced by studies on the glomerular clearance of proteins and dextrans (5-9). In general, molecules smaller than tool wt 68,000 can pass into the urine, whereas those larger are effectively restricted.While physiological studies indicate that the glomerular filter behaves as if it were an isoporous membrane (10), pores conforming to the predicted dimensions have not so far been found in morphological studies of the glomerulus. Ultrastructural studies using particulate tracers, such as saccharated iron oxide (11) and ferritin (tool wt 500,000) (12) have indicated the presence of a filtration barrier at the level of the basement membrane. Graham and Karnovsky (13), using enzyme tracers of different molecular weights (horseradish peroxidase, myeloperoxidase), have suggested that a basement membrane barrier alone cannot explain the glomerular mechanism to prevent protein loss in the' filtrate. This was indicated by the behavior of myeloperoxidase (tool wt 170,000) which crossed the basement membrane but was held back at the epithelial slit pore. On the other hand, the smaller molecule horseradish peroxidase (tool wt 40,000) permeated the basement membrane and passed through the slit pore into the urinary space. These observations have tended to confirm the hypothesis proposed by Hall (14) that the epithelial slit pore represents the filtration * This work was presented in part at the meeting of the American Association of Pathologists and Bacteriologists, San Francisco, Calif., March 1969, and the IVth International Congress of Nephrology,

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confidence: 99%

“…The renal glomerulus effectively restricts plasma proteins and other macromolecules from entering the urinary space (1)(2)(3)(4)(5)(6). Even though this barrier is not absolute, minimal amounts of protein normally leak into Bowman's space (7).…”

mentioning

confidence: 99%

An Ultrastructural Study of Glomerular Permeability Using Catalase and Peroxidase as Tracer Proteins

Venkatachalam

Karnovsky

Fahimi

et al. 1970

The Journal of Experimental Medicine

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“…Even more is this true with the more generally accepted pore size of 50 Á. 5 This finding vitiates Mullins' hypothesis which is based on postulated differences in the ability of the several isomers to fit into the pores of the membrane. In terms of the relationship between molecular size and activity the data of Table I yield no more information than that generally only those BHC molecules are active which have diameters of at least 6 • 5 Á in all directions, and among these the thin molecules (thickness 3 3 and 4•6 Á) are depressant, thick molecules (thickness 6 • 1 Á) convulsant.…”

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confidence: 68%

Structure-Activity Relationship in BHC Stereoisomers

Gerö¹

1959

J. Med. Chem.

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“…Such incomplete tolerance may explain the recent findings of Burstein et al (29), who reported that injection of TNP-OVA and TNP-KLH into mice induced tolerance in IL-2-but not IL-4-producing cells. It is unlikely that a solid tolerant state is induced with OVA conjugates because OVA, with a molecular weight of 39,000, is rapidly cleared from the circulation through the glomerular capillaries before it can adequately diffuse into the extravascular spaces (30)(31)(32) and is thus, at least in the rabbit, a poor tolerogen (30). Likewise, KLH, a large molecule that is rapidly removed from the circulation, does not equilibrate between the intra-and extravascular spaces and requires extremely high and repeated doses to significantly suppress antibody responses in rabbits (33).…”

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confidence: 99%

In vivo induction of tolerance in murine CD4+ cell subsets.

Romball

Weigle

1993

The Journal of Experimental Medicine

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SummaryThe induction of tolerance in mice to preparations of deaggregated human gamma globulin (DHGG) results in in vitro antigen-specific unresponsiveness in CD4 + T cells as well as in both the T helper 1 (Thl) and Th2-1ike subpopulations. Whereas both CD45RB hi and CD45RB l~ cells from lymph nodes of HGG/complete Freund's adjuvant-immunized mice (control) proliferated in vitro to HGG, both subpopulations from mice previously tolerized with DHGG failed to respond. Furthermore, CD4 + T cells from control, but not from DHGG-injected mice, secreted high levels of interleukin 2 (IL-2) after in vitro stimulation with HGG. Although significant levels of IL-4 in supernatants of control CD4 + cells stimulated with HGG were detected in some, but not all, experiments, significant levels of IL-4 were never detected in supernatants of HGGstimulated tolerant CD4 + cells. The demonstration that serum IgG1 anti-HGG is preferentially produced in a few tolerant mice that exhibit a leaky tolerant state suggests that tolerance induction may be more dif~cult to induce in IL-4-than in IL-2-producing cells.A solid and long-lasting tolerant state can be induced in adult mice by a single injection of deaggregated human gamma globulin (DHGG) 1 (for a review see reference 1). Although tolerance is induced in both T and B cells, the dose of tolerogen required for B cell tolerance is 2-3 log10 greater than that for T cell tolerance (for a review see reference 1). The tolerant state in T cells is of long duration, whereas in B cells it is of relatively short duration (2). Induction of tolerance in T cells is independent of the thymus and is not controlled by regulating T cells (3). Although the in vivo induction of tolerance in the T cells can be interfered with by generators of IL-1 or IL-1 itself (4, 5), once induced, the tolerant state cannot be terminated by these reagents. In addition to the in vivo induction of tolerance, tolerance has been induced in HGG-specific T cell clones using either DHGG (6, 7) or inappropriate antigen presentation (8-10). Whereas tolerance in Thl clones is induced in terms of both proliferation and T cell help, tolerance in Th2 clones is induced at only the T helper level (10, 11). Whether the in vivo induction of tolerance occurs in all CD4 + cell populations has recently been questioned. Data have been reported that imply that DHGG induces tolerance in IL-2-producing T cells, but induces responsiveness in IL-4-producing cells, resulting in IL-4 production and T helper activity (12).1Abbreviations used in tkis paper: DHGG, deaggregated human gamma globulin; HGG, human gamma globulin.In this report, the susceptibility of CD4 § cells and their subsets to the induction of tolerance to DHGG was assessed. Our results demonstrate that when mice are exposed to HGG as a tolerogen before immunization, such that the in vitro antigen-specific proliferation of CD4 + T cells is totally abrogated and serum antibody levels are dramatically reduced, antigen-specific proliferation of both Thl-and Th2-1ike subsets is abroga...

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The Passage of Protein Molecules Through the Glomerular Membranes

Cited by 37 publications

References 30 publications

An Ultrastructural Study of Glomerular Permeability Using Catalase and Peroxidase as Tracer Proteins

An Ultrastructural Study of Glomerular Permeability Using Catalase and Peroxidase as Tracer Proteins

Structure-Activity Relationship in BHC Stereoisomers

In vivo induction of tolerance in murine CD4+ cell subsets.

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