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Streptococcal Antibody Probe Crosses the Blood Brain Barrier and Interacts within the Basal Ganglia

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DOI: 10.4236/ojpathology.2015.52007    3,559 Downloads   4,002 Views   Citations

ABSTRACT

Within the brain, the basal ganglia (basal nuclei) regulates wanted movement and inhibits unwanted movement. This area of the brain is intertwined with capillary beds that bring nutrients to the brain and form the blood brain barrier. During disease state, antibodies are increased in circulation and movement of these antibodies into the basal ganglia can occur. Streptococcal infection can lead to the generation of antibodies that have autoimmune activity within the brain. These antibodies have been implicated in neurological disorders. In our laboratory, an in vitro study of a monoclonal mouse antibody generated against the class 1 epitope of the M6 protein has demonstrated binding within the basal ganglia of Lewis rat brains. Here we present an in vivo study using Lewis rats injected with either the streptococcal antibody or an anti-myosin positive control. The interaction and movement of the antibody from blood vessels into the tissues of the basal ganglia was determined through the use of immunofluorescence and fluorescent microscopy and is contrasted with IgG injected and uninjected controls. Our data demonstrates that the streptococcal antibody penetrates the blood brain barrier within 24 hours (as determined by the presence of immunofluorescence outside of blood vessels) and remains significantly elevated above control values even 72 hours after injection (p < 0.05). In contrast, the anti-myosin positive control was not visualized in the interstitial fluid until 48 hours post injection and was no longer significantly above control levels by 72 hours. IgG injected controls did not display movement of antibody into the brain. Therefore, the streptococcal antibody is capable of crossing the blood brain barrier and interacting with tissues of the basal ganglia.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Gebhard, R. , Huff, C. , Osborne, M. , Riegle, L. and Kelly-Worden, M. (2015) Streptococcal Antibody Probe Crosses the Blood Brain Barrier and Interacts within the Basal Ganglia. Open Journal of Pathology, 5, 42-49. doi: 10.4236/ojpathology.2015.52007.

References

[1] Mink, J.W. (2003) The Basal Ganglia and Involuntary Movements: Impaired Inhibition of Competing Motor Patterns. Archives of Neurology, 60, 1365-1368.
http://dx.doi.org/10.1001/archneur.60.10.1365
[2] Church, A.J., Dale, R.C. and Giovannoni, G. (2004) Anti-Basal Ganglia Antibodies: A Possible Dia-gnostic Utility in Idiopathic Movement Disorders? Archives of Disease in Childhood, 89, 611-614.
http://dx.doi.org/10.1136/adc.2003.031880
[3] Martino, D., Church, A.J., Dale, R.C. and Giovannoni, G. (2004) Antibasal Ganglia Antibodies and Their Relevance to Movement Disorders. Current Opinion in Neurology, 17, 425-432.
http://dx.doi.org/10.1097/01.wco.0000137532.76491.19
[4] Kirvan, C.A., Swedo, S.E., Kurahara, D. and Cunningham, M.W. (2006) Streptococcal Mimicry and Antibody-Mediated Cell Signaling in the Pathogenesis of Sydenham’s Chorea. Autoimmunity, 39, 21-29.http://dx.doi.org/10.1080/08916930500484757
[5] Dale, R.C. (2003) Autoimmunity and the Basal Ganglia: New Insights into Old Diseases. QJM, 96, 183-191.http://dx.doi.org/10.1093/qjmed/hcg026
[6] Bronze, M.S. and Dale, J.B. (1993) Epitopes of Streptococcal M Proteins That Evoke Antibodies That Cross-React with Human Brain. Journal of Immunology, 151, 2820-2828.
[7] Jones, K.F., Khan, S.A., Erickson, B.W., Hollingshead, S.K., Scott, J.R. and Fischetti, V.A. (1986) Immunochemical Localization and Amino Acid Sequences of Crossreactive Epitopes within the Group A Streptococcal M6 Protein. Journal of Experimental Medicine, 164, 1226-1238.
http://dx.doi.org/10.1084/jem.164.4.1226
[8] Jones, K.F. and Fischetti, V.A. (1988) The Importance of the Location of Antibody Binding on the M6 Protein for Opsoniation and Phagocytosis of Group A M6 Streptococci. Journal of Experimental Medicine, 167, 1114-1123.http://dx.doi.org/10.1084/jem.167.3.1114
[9] Li, Y., Heuser, J.S., Kosanke, S.D., Hemric, M. and Cunningham, M.W. (2004) Cryptic Epitope Identified in Rat and Human Cardiac Myosin S2 Region Induces Myocarditis in the Lewis Rat. Journal of Immu-nology, 172, 3225-3234.http://dx.doi.org/10.4049/jimmunol.172.5.3225
[10] Kelly-Worden, M., Hammer, L., Gebhard, R., Schrader, L., Griffin, M. and Cooper, D. (2014) ANA Positive Serum from SLE Patients Promotes Cardiovascular and CNS Manifestations in the Lewis Rat. Journal of Pharmacy and Bioallied Science, 6, 198-204. http://dx.doi.org/10.4103/0975-7406.135247
[11] Quinn, A., Ward, K., Fischetti, V.A., Hemric, M. and Cunningham, M.W. (1989) Immunological Relationship between the Class I Epitope of Streptococcal M Protein and Myosin. Infection and Immunity, 66, 4418-4424.
[12] Choi, Y.K. and Kim, K.W. (2008) Blood-Neural Barrier: Its Diversity and Coordinated Cell-to-Cell Communication. BMB Reports, 41, 345-352.
[13] Husby, G., Van De Rijn, I., Zabriskie, J.B., Abdin, Z.H. and Williams Jr., R.C. (1976) Antibodies Reacting with Cytoplasm of Subthalamic and Caudate Nuclei Neurons in Chorea and Acute Rheumatic Fever. Journal of Experimental Medicine, 144, 1094-1110. http://dx.doi.org/10.1084/jem.144.4.1094
[14] Feekes, J.A. and Cassell, M. (2006) The Vascular Supply of the Functional Compartments of the Human Striatum. Brain, 129, 2189-2201. http://dx.doi.org/10.1093/brain/awl158
[15] Pardridge, W.M., Buciak, J.L. and Friden, P.M. (1991) Selective Transport of an Anti-Transferrin Receptor Antibody through the Blood-Brain Barrier in Vivo. Journal of Pharmacology and Experimental Therapeutics, 259, 66-70.
[16] Klibanov, A.L., Martynov, A.V., Slinkin, M.A., Sakharov, I.Y., Smirnov, M.D., Muzykantov, V.R., Danilov, S.M. and Torchilin, V.P. (1988) Blood Clearance of Radiolabeled Antibody: Enhancement by Lactosamination and Treatment with Biotin-Avidin or Anti-Mouse IgG Antibodies. Journal of Nuclear Medicine, 29, 1951-1956.
[17] Szentistvanyii, I., Patlak, C.S., Ellis, R.A. and Cserr, H.F. (1984) Drainage of Interstitial Fluid from Different Regions of Rat Brain. American Journal of Physiology. Renal Physiology, 246, F835-F844.
[18] Ohata, K. and Marmarou, A. (1992) Clearance of Brain Edema and Macromolecules through the Cortical Extracellular Space. Journal of Neurosurgery, 77, 387-396.
http://dx.doi.org/10.3171/jns.1992.77.3.0387
[19] Nakagawa, S., Deli, M.A., Kawaguchi, H., Shimizudani, T., Shimono, T., Kittel, A., Tanaka, K. and Niwa, M. (2009) A New Blood-Brain Barrier Model Using Primary Rat Brain Endothelial Cells, Pericytes and Astrocytes. Neurochemistry International, 54, 253-263.
http://dx.doi.org/10.1016/j.neuint.2008.12.002
[20] Bernacki, J., Dobrowolska, A., Nierwińska, K. and MaIecki, A. (2008) Physiology and Pharmacological Role of the Blood-Brain Barrier. Pharmacological Reports, 60, 600-622.
[21] Nishioku, T., Dohgu, S., Takata, F., Eto, T., Ishikawa, N., Kodama, K.B., Nakagawa, S., Yamauchi, A. and Kataoka, Y. (2009) Detachment of Brain Pericytes from the Basal Lamina Is Involved in Disruption of the Blood-Brain Barrier Caused by Lipopolysaccharide-Induced Sepsis in Mice. Cellular and Molecular Neurobiology, 29, 309-316.
[22] Kelly-Worden, M., Eisa, A., Huff, C. and Osborne, M. (2013) Streptococcal Anti-Phospholipid Antibody, mAB10F5, Binds Greatest in the Cardiac Valve Region. Biophysical Journal, 104, 154a.
http://dx.doi.org/10.1016/j.bpj.2012.11.872
[23] Kelly-Worden, M., Osborne, M. and Gebhard, R. (2012) mAb10F5 Is an Anti-Phospholipid Antibody that Binds in the Basal Ganglia in Vivo. Biophysical Journal, 102, 496a.
http://dx.doi.org/10.1016/j.bpj.2011.11.2718

  
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