Summary
The concentration ratios of several proteins between serum and cerebrospinal fluid (CSF) can be correlated more easily to hydrodynamic volumes than to molweights. Hydrodynamic radii were calculated from literature diffusion data and determined by analytical column chromatography and gel electrophoresis. Discrepancies between molweight and hydrodynamic volume become evident, especially with the high-molecular proteins because of stronger conformational variability in this size range. The permeability of the blood-CSF-barrier is compared to the blood-lymph-barrier and the results are discussed with reference to current views about capillary permeability. The basement membrane, exposed to the capillary lumen by endothelial fenestrations is considered the most likely site of protein passage at the blood-CSF-barrier.
Zusammenfassung
Die Konzentrations-Quotienten zahlreicher Proteine zwischen Serum und Liquor cerebrospinalis korrelieren besser mit den hydrodynamischen Volumen als mit den Molekulargewichten. Die hydrodynamischen Radien wurden der Literatur entnommen, sowie mit Hilfe der analytischen Säulenchromatographie und Gelelektrophorese bestimmt. Diskrepanzen zwischen Molekulargewicht und hydrodynamischem Volumen werden vorwiegend bei den großmolekularen Proteinen gefunden, da hier die Molekülformen stärker variieren. Die Permeabilität der Blut-Liquor-Schranke wird mit der Blut-Lymph-Schranke verglichen, und die Daten werden unter dem Aspekt der derzeitigen Filtrationstheorien diskutiert. Die Basalmembran, die durch Endothelfenster direkten Kontakt mit dem Kapillarlumen erhält, ist der wahrscheinlichste Ort für den Proteindurchtritt an der Blut-Liquor-Schranke.
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References
Andrews, P.: The gel-filtration behaviour of proteins related to their molecular weights over a wide range. Biochem. J.96, 595 (1965)
Andrews, P.: Estimation of molecular size and molecular weights of biological compounds by gel filtration. Meth. Biochem. Anal.18, 1 (1970)
Arturson, G., Granath, K.: Dextrans as test molecules in studies of the functional ultrastructure of biological membranes. Clin. chim. Acta37, 309 (1972)
Berlet, H. H., Pilz, H.: Die Bedeutung von Plasmakreatin und neurologischen Erkrankungen für den Kreatingehalt im Liquor cerebrospinalis beim Menschen. Z. ges. Neurol. Psychiat.201, 310 (1972)
Bock, E.: In: A Manual of quantitative immuno-electrophoresis. Eds.: Axelsen, N. H., Krøll, J., Weeke, B., p. 111. Oslo: Universitetsforlaget 1973
Bradbury, M. W. B., Stulcova, B.: Efflux mechanism contributing to the stability of the potassium concentration in cerebrospinal fluid. J. Physiol. (Lond.)208, 415 (1970)
Brightman, M. W., Klatzo, I., Olsson, Y., Reese, T. S.: The blood-brain-barrier to proteins under normal and pathological conditions. J. Neurol. Sci.10, 215 (1970)
Brightman, M. W., Reese, T. S., Feder, N.: Assessment with the electron microscope of the permeability to peroxidase of cerebral endothelium and epithelium in mice and sharks. In: Ref. 13, p. 468
Bryce, C. F. A., Crichton, R. R.: The subunit structure of horse spleen apoferritin. J. biol. Chem.246, 4198 (1971)
Clausen, J.: The β-lipoprotein of serum and cerebrospinal fluid. Acta neurol. scand.42, 153 (1966)
Clementi, F., Palade, G. E.: Intestinal capillaries. I. Permeability to peroxydase and ferritin. J. Cell Biol.41, 33 (1969)
Cohen, M. W., Gerschenfeld, H. M., Kuffler, S. W.: Ionic environment of neurones and glial cells in the brain of an amphibian. J. Physiol. (Lond.)197, 363 (1968)
Crone, Ch., Lassen, N. A.: Capillary permeability. Copenhagen: Munksgaard 1970
Crone, C., Thompson, A. M.: Permeability of brain capilaries. In: Ref. 13, p. 447
Cserr, H.: Potassium exchange between cerebrospinal fluid, plasma and brain. Amer. J. Physiol.209, 1219 (1965)
Davson, H.: Physiology of the cerebrospinal fluid. London: Churchill, Ltd. 1967
Dohrmann, G. J., Bucy, P. C.: Human choroid plexus: a light and electron microscopic study. J. Neurosurg.33, 506 (1970)
Dunn, J. S., Wyburn, G. M.: The anatomy of the bloodbrain barrier: a review. Scot. med. J.17, 21 (1972)
Felgenhauer, K.: Moleculat size of human serum proteins determined by exclusion gel electrophoresis. Clin. chim. Acta32, 53 (1971)
Felgenhauer, K.: Evaluation of molecular size in gelelectrophoretic techniques. Hoppe Seylers Z. physiol. Chem. (1974) (in press)
Felgenhauer, K., Engel, H., Rapic, N., Schliep, G.: Rapid concentration of small volumes of protein solution. Z. klin. Chem. klin. Biochem.11, 173 (1973)
Felgenhauer, K., Graesslin, D., Huismans, B. D.: Comparison of slab and cylinder gel focusing. Prot. Biol. Fluids19, 575 (1971)
Forster, R. E.: In: Current topics in membranes and transport. Eds.: Bronner, F., and Kleinzeller, A., II, p. 41. New York, London: Acad. Press 1971
Frick, E.: Quantitative Bestimmung des Transferrins im normalen und pathologischen Liquor cerebrospinalis. Klin. Wschr.41, 75 (1963)
Frick, E.: Barriers of the central nervous system and physiology of proteins. Int. Ophthal. Clinics5, 683 (1965)
Gottesleben, A., Bauer, H. J.: Quantitative Immunochemie der Liquorproteine bei entzündlichen Erkrankungen des Nervensystems. Germ. med. Mth.12, 331 (1967)
Greenstein, J. P., Winitz, M.: Chemistry of the amino acids, I. p. 467. New York: Wiley Inc. 1961
Guroff, G.: In: Basic neurochemistry, eds.: R. W. Alberset al. p. 191. Boston: Little, Brown and Co. 1972
Hurliman, J., Waldesbühl, M., Zuber, C.: Human salivary immunoglobulin A. Biochim. biophys. Acta (Amst.)181, 393 (1969)
Jost, W.: Fundamental aspects of diffusion processes. Angew. Chemie (Internat. edit.)3, 713 (1964)
Karnovsky, M. J.: Morphology of capillaries with special reference to muscle capillaries. In: Ref. 13, p. 341
Katzmann, R.: Blood-brain-CSF barriers. In: Ref. 28, p. 327
Kefalides, N. A.: Chemical properties of basement membranes. In: Int. Rev. exp. Path.10, 1 (1972)
Klotz, I. M., Darnall, D. W.: Protein subunits: a table. Science166, 126 (1969)
Lajtha, A., Ford, D. H. (eds.): Brain barrier systems. Amsterdam: Elsevier Publ. Co. 1968
Landis, E. M., Pappenheimer, J. R.: Exchange of substances through capillary walls. Handbook of physiology, circulation, vol. II, p. 961. Baltimore: Williams and Wilkins 1963
Laurent, T. C.: The structure and function of the intercellular polysaccharides in connective tissue. In: Ref. 13, p. 261
Laurent, T. C., Killander, J.: A theory of gel filtration and its experimental verification. J. Chromatogr.14, 317 (1964)
Laurrell, C.-B.: Electroimmuno assay. Scand. J. clin. Lab. Invest.29, Suppl. 124, 21 (1972)
Levy, R. J., Bilheimer, D. W., Eisenberg, S.: In: Plasma proteins (ed. R. M. S. Smellie). London-New York: Acad. Press 1971
Lieb, W. R., Stein, W. D.: The molecular basis of simple diffusion within biological membranes. In: Current topics in membranes and transport2, 1 (1971)
Link, H., Zettervall, O., Blennow, G.: Individual cerebrospinal fluid (CSF) proteins in the evaluation of increased CSF total protein. Z. ges. Neurol. Psychiat.203, 119 (1972)
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. biol. Chem.193, 265 (1951)
Lüscher, E. F.: The biochemical properties and the biological function of fibrinogen. Prot. Biol. Fluids14, 1 (1966)
Manuel, Y., Revillard, J. P., Betuel, H.: Proteins in normal and pathological urine. Basel: S. Karger 1970
Mc.Ilwain, H., Bachelard, H. S.: Biochemistry and the central nervous system. Edinburgh: Churchill Livingstone 1971
Oldendorf, W. H.: Brain uptake of radiolabeled amino acids, amines and hexoses after arterial injection. Amer. J. Physiol.221, 1629 (1971)
Pappenheimer, J. R.: The ionic composition of cerebral extracellular fluid and its relation to control breathing. Harvey Lect.61, 71 (1967)
Peeters, H. (ed.): Urinary proteins. Prot. Biol. Fluids21, 341–561 (1973)
Putnam, F. W. (ed.): The proteins. New York: Acad. Press 1966
Rask, L., Peterson, P. A.: Structure and function of the retinol-binding protein: a protein characteristic of tubular proteinuria. Prot. Biol. Fluids21, 485 (1973)
Rauen, H. W. (ed.): Biochemisches Taschenbuch. Berlin-Heidelberg-New York: Springer 1964
Reese, T. S., Karnovsky, M. J.: Fine structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol.34, 207 (1967)
Renkin, E. M.: Filtration, diffusion and molecular sieving through porous cellulose membranes. J. gen. Physiol.38, 225 (1955)
Renkin, E. M.: Stofftransport durch die Wände von Blutkapillaren. Klin. Wschr.41, 147 (1963)
Renkin, E. M.: Permeability and molecular size in “peripheral” and glomerular capillaries. In: Ref. 13, p. 544
Rosenthal, F. D., Soothill, J. F.: An immunochemical study of the proteins in cerebrospinal fluid. J. Neurol. Neurosurg. Psychiat.25, 177 (1962)
Schliep, G., Felgenhauer, K.: The α2-macroglobulin level in cerebrospinal fluid, a parameter for the condition of the blood-CSF-barrier. J. Neurol.207, 171 (1974)
Schliep, G., Rapic, N., Felgenhauer, K.: Quantitation of high-molecular proteins in cerebrospinal fluid. Z. klin. Chem. klin. Biochem.12, 367 (1974)
Schmidt, R. M.: Der Liquor cerebrospinalis. Berlin: VEB Verlag und Gesundheit, 1968
Schultze, H. E., Heremans, J. F.: Molecular biology of human proteins, vol. I, Amsterdam: Elsevier 1966
Siegel, L. M., Monty, K. J.: Determination of molecular weights and frictional ratios of proteins in impure systems by use of gel filtration and density gradient centrifugation. Biochim. biophys. Acta (Amst.)112, 346 (1966)
Slater, G. G.: Pore-limit electrophoresis on a gradient of polyacrylamide gel. Analyt. Biochem.24, 215 (1968)
Snodgrass, S. R., Cutler, R. W. P., Kang, E. S., Lorenzo, A. V.: Transport of neutral amino acids from feline cerebrospinal fluid. Amer. J. Physiol.217, 974 (1969)
Sober, H. A. (ed.) Handbook of biochemistry. Cleveland: The Chemical Rubber Co. 1970.
Svehag, S. E., Chesebro, B., Bloth, B.: Ultrastructure of gamma M immunoglobulin and alpha-2-macroglobulin: Electron-microscopic study. Science158, 933 (1967)
Weeke, B.: Quantitative estimation of human immunoglobulins following carbamylation by electrophoresis in antibody-containing agarose. Scand. J. clin. Lab. Invest.22, 107 (1968)
West, E. St.: Textbook of biophysical chemistry. New York: MacMillan Co. 1963
Wyke, B.: Brain function and metabolic disorders. London: Butterworths 1963
Yudilevich, D. L., De Rose, N., Sepulveda, F. V.: Facilitated transport of amino acids through the blood-brain-barrier of the dog studied in a single capillary circulation. Brain Res.44, 569 (1972)
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Dedicated to Prof. W. Scheid on the occasion of his 65th birthday.
I thank Dr. W. R. Lieb, London, for the helpful discussion of amino acid data.
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Felgenhauer, K. Protein size and cerebrospinal fluid composition. Klin Wochenschr 52, 1158–1164 (1974). https://doi.org/10.1007/BF01466734
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DOI: https://doi.org/10.1007/BF01466734
Key words
- Blood-brain-barrier
- capillary permeability
- cerebrospinal fluid
- electrophoresis
- polyacrylamide gel
- gel filtration
- immunoassay
- protein conformation