Internalization of bevacizumab by retinal endothelial cells and its intracellular fate: Evidence for an involvement of the neonatal Fc receptor

Experimental Eye Research

Volumn 143, Issue , 2016, Pages 49-59

  Deissler, Heidrun L ^a   Lang, Gerhard K ^a   Lang, Gabriele E ^a  

^a UNIVERSITY OF ULM   (Germany)

Author keywords

Antibody internalization; Bevacizumab; Neonatal Fc receptor (FcRn); Retinal endothelial cells; Transport

Indexed keywords

ALPHA TUBULIN; BEVACIZUMAB; FC RECEPTOR; NEONATAL FC RECEPTOR; PROTEIN A; UNCLASSIFIED DRUG; VIMENTIN; ANGIOGENESIS INHIBITOR; BOVINE SERUM ALBUMIN; CYTOSKELETON PROTEIN; FC RECEPTOR, NEONATAL; HLA ANTIGEN CLASS 1; SERUM-FREE MEDIUM;

ANIMAL CELL; ARTICLE; BOVINE; CAPILLARY ENDOTHELIAL CELL; CELL IMMORTALIZATION; CONTROLLED STUDY; CYTOSKELETON; DRUG RECEPTOR BINDING; DRUG UPTAKE; ENDOSOME; EXOCYTOSIS; IMMUNOFLUORESCENCE TEST; INTERNALIZATION; INTRACELLULAR TRANSPORT; MONOLAYER CULTURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RETINA CELL; RETINAL ENDOTHELIAL CELL; SERUM; TEMPERATURE DEPENDENCE; TRANSCYTOSIS; ACTIVE TRANSPORT; ANIMAL; CELL LINE; CELL MOTION; CELL PROLIFERATION; CYTOPLASM; ENDOTHELIUM CELL; INDIRECT FLUORESCENT ANTIBODY TECHNIQUE; METABOLISM; PHYSIOLOGY; RETINA BLOOD VESSEL; SERUM-FREE MEDIUM; TEMPERATURE; WESTERN BLOTTING;

ANGIOGENESIS INHIBITORS; ANIMALS; BEVACIZUMAB; BIOLOGICAL TRANSPORT, ACTIVE; BLOTTING, WESTERN; CATTLE; CELL LINE; CELL MOVEMENT; CELL PROLIFERATION; CULTURE MEDIA, SERUM-FREE; CYTOPLASM; CYTOSKELETAL PROTEINS; ENDOTHELIAL CELLS; FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT; HISTOCOMPATIBILITY ANTIGENS CLASS I; RECEPTORS, FC; RETINAL VESSELS; SERUM ALBUMIN, BOVINE; TEMPERATURE;

EID: 84945300064     PISSN: 00144835     EISSN: 10960007     Source Type: Journal    
DOI: 10.1016/j.exer.2015.10.007     Document Type: Article

References (47)

1. Aboul Naga S.H., Dithmer M., Chitadze G., Kabelitz D., Lucius R., Roider J., Klettner A. Intracellular pathways following uptake of bevacizumab in RPE cells. Exp. Eye Res. 2015, 131:29-41. 10.1016/j.exer.2014.12.010.
2. Allan V. Microtubule motors: moving forward on many fronts. F1000 Biol. Rep. 2009, 1:52. 10.3410/B1-52.
3. Antohe F., Rădulescu L., Gafencu A., Gheţie V., Simionescu M. Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells. Hum. Immunol. 2001, 62:93-105. 10.1016/S0198-8859(00)00244-5.
4. Arevalo J.F., Sanchez J.G., Lasave A.F., Wu L., Maia M., Bonafonte S., Brito M., Alezzandrini A.A., Restrepo N., Berrocal M.H., Saravia M., Farah M.E., Fromow-Guerra J., Morales-Canton V. Intravitreal bevacizumab (Avastin) for diabetic retinopathy: the 2010 GLADAOF lecture. J. Ophthalmol. 2011, Article ID 584238. 10.1155/2011/584238 584238:1-13.
5. Cui D., Zhang L., Li J., Zhao Y., Hu X., Dai Y., Zhang R., Li N. Bovine FcRn-mediated human immunoglobulin G transfer across the milk-blood barrier in transgenic mice. PLoS One 2014, 9:e115972. 10.1371/journal.pone.0115972.
6. Dave J.M., Bayless K.J. Vimentin as an integral regulator of cell adhesion and endothelial sprouting. Microcirculation 2014, 21:333-344. 10.1111/micc.12111.
7. Deissler H., Deissler H., Lang G.K., Lang G.E. Generation and characterization of iBREC: novel hTERT-immortalized bovine retinal endothelial cells. Int. J. Mol. Med. 2005, 15:65-70. 10.3892/ijmm.16.1.65.
8. Deissler H., Deissler H., Lang S., Lang G.E. VEGF-induced effects on proliferation, migration and tight junctions are restored by ranibizumab (Lucentis®) in microvascular retinal endothelial cells. Br. J. Ophthalmol. 2008, 92:839-843. 10.1136/bjo.2007.135640.
9. Deissler H.L., Deissler H., Lang G.E. Inhibition of VEGF is sufficient to completely restore barrier malfunction induced by growth factors in microvascular retinal endothelial cells. Br. J. Ophthalmol. 2011, 95:1151-1156. 10.1136/bjo.2010.192229.
10. Deissler H.L., Deissler H., Lang G.E. Actions of bevacizumab and ranibizumab on microvascular retinal endothelial cells: similarities and differences. Br. J. Ophthalmol. 2012, 96:1023-1028. 10.1136/bjophthalmol-2012-301677.
11. Deissler H.L., Lang G.K., Lang G.E. VEGF but not PlGF disturbs the barrier of retinal endothelial cells. Exp. Eye Res. 2013, 115:162-171. 10.1016/j.exer.2013.07.018.
12. Deissler H.L., Lang G.K., Lang G.E. Capacity of aflibercept to counteract VEGF-stimulated abnormal behavior of retinal microvascular endothelial cells. Exp. Eye Res. 2014, 122:20-31. 10.1016/j.exer.2014.02.024.
13. Do D.V., Nguyen Q.D., Boyer D., Schmidt-Erfurth U., Brown D.M., Vitti R., Berliner A.J., Gao B., Zeitz O., Ruckert R., Schmelter T., Sandbrink R., Heier J.S. One-year outcomes of the DA VINCI Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology 2012, 119:1658-1665. DA VINCI Study Group. 10.1016/j.ophtha.2012.02.010.
14. Feng Y., Venema V.J., Venema R.C., Tsai N., Behzadian M.A., Caldwell R.B. VEGF-induced permeability increase is mediated by caveolae. Investig. Ophthalmol. Vis. Sci. 1999, 40:157-167.
15. Ferrara N., Damico L., Shams N., Lowman H., Kim R. Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina 2006, 26:859-870. 10.1097/01.iae.0000242842.14624.e7.
16. Fujii H., Nakatani K., Arita N., Ito M.R., Terada M., Miyazaki T., Yoshida M., Ono M., Fujiwara T., Saiga K., Ota T., Ohtani H., Lockwood M., Sasaki T., Nose M. Internalization of antibodies by endothelial cells via fibronectin implicating a novel mechanism in lupus nephritis. Kidney Int. 2003, 64:1662-1670. 10.1046/j.1523-1755.2003.00252.x.
17. Goebl N.A., Babbey C.M., Datta-Mannan A., Witcher D.R., Wroblewski V.J., Dunn K.W. Neonatal Fc receptor mediates internalization of Fc in transfected human endothelial cells. Mol. Biol. Cell. 2008, 19:5490-5505. 10.1091/mbc.E07-02-0101.
18. Harhaj N.S., Felinski E.A., Wolpert E.B., Sundstrom J.M., Gardner T.W., Antonetti D.A. VEGF activation of protein kinase C stimulates occludin phosphorylation and contributes to endothelial permeability. Investig. Ophthalmol. Vis. Sci. 2006, 47:5106-5115. 10.1167/iovs.06-0322.
19. Hofman P., Blaauwgeers H.G., Tolentino M.J., Adamis A.P., Nunes Cardozo B.J., Vrensen G.F., Schlingemann R.O. VEGF-A induced hyperpermeability of blood-retinal barrier endothelium in vivo is predominantly associated with pinocytotic vesicular transport and not with formation of fenestrations. Curr. Eye Res. 2000, 21:637-645.
20. Holash J., Davis S., Papadopoulos N., Croll S.D., Ho L., Russell M., Boland P., Leidich R., Hylton D., Burova E., Ioffe E., Huang T., Radziejewski C., Bailey K., Fandl J.P., Daly T., Wiegand S.J., Yancopoulos G.D., Rudge J.S. VEGF-trap: a VEGF blocker with potent antitumor effects. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:11393-11398. 10.1073/pnas.172398299.
21. Jerdeva G.V., Tesar D.B., Huey-Tubman K.E., Ladinsky M.S., Fraser S.E., Bjorkman P.J. Comparison of FcRn- and pIgR-mediated transport in MDCK cells by fluorescence confocal microscopy. Traffic 2010, 11:1205-1220. 10.1111/j.1600-0854.2010.01083.x.
22. Julien S., Biesemeier A., Taubitz T., Schraermeyer U. Different effects of intravitreally injected ranibizumab and aflibercept on retinal and choroidal tissues of monkey eyes. Br. J. Ophthalmol. 2014, 98:813-825. 10.1136/bjophthalmol-2013-304019.
23. 2-microglobulin-containing neonatal intestinal transport receptor. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:5512-5516.
24. Kacskovics I., Wu Z., Simister N.E., Frenyó L.V., Hammarström L. Cloning and characterization of the bovine MHC class I-like Fc receptor. J. Immunol. 2000, 164:1889-1897.
25. Kacskovics I., Kis Z., Mayer B., West A.P., Tiangco N.E., Tilahun M., Cervenak L., Bjorkman P.J., Goldsby R.A., Szenci O., Hammarström L. FcRn mediates elongated serum half-life of human IgG in cattle. Int. Immunol. 2006, 18:525-536. 10.1093/intimm/dxh393.
26. Kim H., Fariss R.N., Zhang C., Robinson S.B., Thill M., Csaky K.G. Mapping of the neonatal Fc receptor in the rodent eye. Investig. Ophthalmol. Vis. Sci. 2008, 49:2025-2029. 10.1167/iovs.07-0871.
27. Kim H., Robinson S.B., Csaky K.G. FcRn receptor-mediated pharmacokinetics of therapeutic IgG in the eye. Mol. Vis. 2009, 15:2803-2812.
28. Klettner A., Kruse M.L., Meyer T., Wesch D., Kabelitz D., Roider J. Different properties of VEGF-antagonists: bevacizumab but not Ranibizumab accumulates in RPE cells. Graefes Arch. Clin. Exp. Ophthalmol. 2009, 247:1601-1608. 10.1007/s00417-009-1136-0.
29. Klettner A., Möhle F., Roider J. Intracellular Bevacizumab reduces phagocytotic uptake in RPE cells. Graefes Arch. Clin. Exp. Ophthalmol. 2010, 248:819-824. 10.1007/s00417-010-1317-x.
30. Klettner A., Tahmaz N., Dithmer M., Richert E., Roider J. Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis. Br. J. Ophthalmol. 2014, 98:1448-1452. 10.1136/bjophthalmol-2014-305105.
31. Kobayashi T., Vischer U.M., Rosnoblet C., Lebrand C., Lindsay M., Parton R.G., Kruithof E.K., Gruenberg J. The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells. Mol. Biol. Cell 2000, 11:1829-1843. 10.1091/mbc.11.5.1829.
32. Lang G.E., Berta A., Eldem B.M., Simader C., Sharp D., Holz F.G., Sutter F., Gerstner O., Mitchell P. Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study. Ophthalmology 2013, 120:2004-2012. RESTORE Extension Study Group. 10.1016/j.ophtha.2013.02.019.
33. Lang G.E., Lang G.K., Deissler H.L. Treatment of diabetic macular edema with the VEGF inhibitors ranibizumab and bevacizumab: conclusions from basic in vitro studies. Klin. Monbl. Augenheilkd 2014, 231:527-534. 10.1055/s-0033-1360360.
34. Mitchell P., Bandello F., Schmidt-Erfurth U., Lang G.E., Massin P., Schlingemann R.O., Sutter F., Simader C., Burian G., Gerstner O., Weichselberger A. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 2011, 118:615-625. RESTORE study group. 10.1016/j.ophtha.2011.01.031.
35. Nilson B.H., Lögdberg L., Kastern W., Björck L., Akerström B. Purification of antibodies using protein L-binding framework structures in the light chain variable domain. J. Immunol. Methods 1993, 164:33-40. 10.1016/0022-1759(93)90273-A.
36. Ober R.J., Radu C.G., Ghetie V., Ward E.S. Differences in promiscuity for antibody-FcRn interactions across species: implications for therapeutic antibodies. Int. Immunol. 2001, 13:1551-1559. 10.1093/intimm/13.12.1551.
37. Ober R.J., Martinez C., Lai X., Zhou J., Ward E.S. Exocytosis of IgG as mediated by the receptor, FcRn: an analysis at the single-molecule level. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:11076-11081. 10.1073/pnas.0402970101.
38. Pappenheimer J.R., Renkin E.M., Borrero L.M. Filtration, diffusion and molecular sieving through peripheral capillary membranes; a contribution to the pore theory of capillary permeability. Am. J. Physiol. 1951, 167:13-46.
39. Presta L.G., Chen H., O'Connor S.J., Chisholm V., Meng Y.G., Krummen L., Winkler M., Ferrara N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997, 57:4593-4599.
40. Powner M.B., McKenzie J.A.G., Christianson G.J., Derry C., Roopenian D.C., Fruttiger M. Expression of neonatal Fc receptor in the eye. Investig. Ophthalmol. Vis. Sci. 2014, 55:1607-1615. 10.1167/iovs.13-12574.
41. Raghavan M., Chen M.Y., Gastinel L.N., Bjorkman P.J. Investigation of the interaction between the class I MHC-related Fc receptor and its immunoglobulin G ligand. Immunity 1994, 1:303-315. 10.1016/1074-7613(94)90082-5.
42. Sand K.M., Bern M., Nilsen J., Noordzij H.T., Sandlie I., Andersen J.T. Unraveling the interaction between FcRn and albumin: opportunities for design of albumin-based therapeutics. Front. Immunol. 2015, 5:682. 10.3389/fimmu.2014.00682.
43. Schraermeyer U., Julien S. Formation of immune complexes and thrombotic microangiopathy after intravitreal injection of bevacizumab in the primate eye. Graefes Arch. Clin. Exp. Ophthalmol. 2012, 250:1303-1313. 10.1007/s00417-012-2055-z.
44. Stewart E.A., Samaranayake G.J., Browning A.C., Hopkinson A., Amoaku W.M. Comparison of choroidal and retinal endothelial cells: characteristics and response to VEGF-isoforms and anti-VEGF treatment. Exp. Eye Res. 2011, 93:761-766. 10.1016/j.exer.2011.09.010.
45. Sun M., Fu H., Cheng H., Cao Q., Zhao Y., Mou X., Zhang X., Liu X., Ke Y. A dynamic real-time method for monitoring epithelial barrier function in vitro. Anal. Biochem. 2012, 425:96-103. 10.1016/j.ab.2012.03.010.
46. Ward E.S., Martinez C., Vaccaro C., Zhou J., Tang Q., Ober R.J. From sorting endosomes to exocytosis: association of Rab4 and Rab11 GTPases with the Fc receptor, FcRn, during recycling. Mol. Biol. Cell 2005, 16:2028-2038. 10.1091/mbc.E04-08-0735.
47. Wines B.D., Powell M.S., Parren P.W., Barnes N., Hogarth P.M. The IgG Fc contains distinct Fc receptor (FcR) binding sites: the leukocyte receptors Fc gamma RI and Fc gamma RIIa bind to a region in the Fc distinct from that recognized by neonatal FcR and protein A. J. Immunol. 2000, 164:5313-5818. 10.4049/jimmunol.164.10.5313.