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Open Access 01-12-2013 | Research

Transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal fluid barrier after bacterial infection in vitro

Authors: Ulrike Steinmann, Julia Borkowski, Hartwig Wolburg, Birgit Schröppel, Peter Findeisen, Christel Weiss, Hiroshi Ishikawa, Christian Schwerk, Horst Schroten, Tobias Tenenbaum

Published in: Journal of Neuroinflammation | Issue 1/2013

Abstract

Background

Bacterial invasion through the blood-cerebrospinal fluid barrier (BCSFB) during bacterial meningitis causes secretion of proinflammatory cytokines/chemokines followed by the recruitment of leukocytes into the CNS. In this study, we analyzed the cellular and molecular mechanisms of polymorphonuclear neutrophil (PMN) and monocyte transepithelial transmigration (TM) across the BCSFB after bacterial infection.

Methods

Using an inverted transwell filter system of human choroid plexus papilloma cells (HIBCPP), we studied leukocyte TM rates, the migration route by immunofluorescence, transmission electron microscopy and focused ion beam/scanning electron microscopy, the secretion of cytokines/chemokines by cytokine bead array and posttranslational modification of the signal regulatory protein (SIRP) α via western blot.

Results

PMNs showed a significantly increased TM across HIBCPP after infection with wild-type Neisseria meningitidis (MC58). In contrast, a significantly decreased monocyte transmigration rate after bacterial infection of HIBCPP could be observed. Interestingly, in co-culture experiments with PMNs and monocytes, TM of monocytes was significantly enhanced. Analysis of paracellular permeability and transepithelial electrical resistance confirmed an intact barrier function during leukocyte TM. With the help of the different imaging techniques we could provide evidence for para- as well as for transcellular migrating leukocytes. Further analysis of secreted cytokines/chemokines showed a distinct pattern after stimulation and transmigration of PMNs and monocytes. Moreover, the transmembrane glycoprotein SIRPα was deglycosylated in monocytes, but not in PMNs, after bacterial infection.

Conclusions

Our findings demonstrate that PMNs and monoctyes differentially migrate in a human BCSFB model after bacterial infection. Cytokines and chemokines as well as transmembrane proteins such as SIRPα may be involved in this process.

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Kim KS: Acute bacterial meningitis in infants and children. Lancet Infect Dis 2010, 10:32–42.CrossRefPubMed

Tenenbaum T, Papandreou T, Gellrich D, Friedrichs U, Seibt A, Adam R, Wewer C, Galla HJ, Schwerk C, Schroten H: Polar bacterial invasion and translocation of Streptococcus suis across the blood-cerebrospinal fluid barrier in vitro. Cell Microbiol 2009, 11:323–336.CrossRefPubMed

Tenenbaum T, Matalon D, Adam R, Seibt A, Wewer C, Schwerk C, Galla HJ, Schroten H: Dexamethasone prevents alteration of tight junction-associated proteins and barrier function in porcine choroid plexus epithelial cells after infection with Streptococcus suis in vitro. Brain Res 2008, 1229:1–17.CrossRefPubMed

Matter K, Balda MS: Epithelial tight junctions, gene expression and nucleo-junctional interplay. J Cell Sci 2007, 120:1505–1511.CrossRefPubMed

Matter K, Balda MS: Signalling to and from tight junctions. Nat Rev Mol Cell Biol 2003, 4:225–236.CrossRefPubMed

Swartley JS, Marfin AA, Edupuganti S, Liu LJ, Cieslak P, Perkins B, Wenger JD, Stephens DS: Capsule switching of Neisseria meningitidis. Proc Natl Acad Sci USA 1997, 94:271–276.CrossRefPubMedPubMedCentral

Melican K, Dumenil G: Vascular colonization by Neisseria meningitidis. Curr Opin Microbiol 2012, 15:50–56.CrossRefPubMed

Pron B, Taha MK, Rambaud C, Fournet JC, Pattey N, Monnet JP, Musilek M, Beretti JL, Nassif X: Interaction of Neisseria maningitidis with the components of the blood–brain barrier correlates with an increased expression of PilC. J Infect Dis 1997, 176:1285–1292.CrossRefPubMed

Stephens DS: Biology and pathogenesis of the evolutionarily successful, obligate human bacterium Neisseria meningitidis. Vaccine 2009,27(Suppl 2):B71–77.CrossRefPubMedPubMedCentral

10.

Schwerk C, Papandreou T, Schuhmann D, Nickol L, Borkowski J, Steinmann U, Quednau N, Stump C, Weiss C, Berger J, Wolburg H, Claus H, Vogel U, Ishikawa H, Tenenbaum T, Schroten H: Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier. PLoS One 2012, 7:e30069.CrossRefPubMedPubMedCentral

11.

Ransohoff RM, Kivisakk P, Kidd G: Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 2003, 3:569–581.CrossRefPubMed

12.

Wittchen ES: Endothelial signaling in paracellular and transcellular leukocyte transmigration. Front Biosci 2009, 14:2522–2545.CrossRef

13.

Chin AC, Parkos CA: Pathobiology of neutrophil transepithelial migration: implications in mediating epithelial injury. Annu Rev Pathol 2007, 2:111–143.CrossRefPubMed

14.

Muller WA: Mechanisms of leukocyte transendothelial migration. Annu Rev Pathol 2011, 6:323–344.CrossRefPubMedPubMedCentral

15.

Engelhardt B, Wolburg H: Mini-review: Transendothelial migration of leukocytes: through the front door or around the side of the house? Eur J Immunol 2004, 34:2955–2963.CrossRefPubMed

16.

Wewer C, Seibt A, Wolburg H, Greune L, Schmidt MA, Berger J, Galla HJ, Quitsch U, Schwerk C, Schroten H, Tenenbaum T: Transcellular migration of neutrophil granulocytes through the blood-cerebrospinal fluid barrier after infection with Streptococcus suis. J Neuroinflammation 2011, 8:51.CrossRefPubMedPubMedCentral

17.

Cooper D, Lindberg FP, Gamble JR, Brown EJ, Vadas MA: Transendothelial migration of neutrophils involves integrin-associated protein (CD47). Proc Natl Acad Sci USA 1995, 92:3978–3982.CrossRefPubMedPubMedCentral

18.

Seiffert M, Cant C, Chen Z, Rappold I, Brugger W, Kanz L, Brown EJ, Ullrich A, Buhring HJ: Human signal-regulatory protein is expressed on normal, but not on subsets of leukemic myeloid cells and mediates cellular adhesion involving its counterreceptor CD47. Blood 1999, 94:3633–3643.PubMed

19.

Lahoud MH, Proietto AI, Gartlan KH, Kitsoulis S, Curtis J, Wettenhall J, Sofi M, Daunt C, O'Keeffe M, Caminschi I: Signal regulatory protein molecules are differentially expressed by CD8- dendritic cells. J Immunol 2006, 177:372–382.CrossRefPubMed

20.

Vernon-Wilson EF, Kee WJ, Willis AC, Barclay AN, Simmons DL, Brown MH: CD47 is a ligand for rat macrophage membrane signal regulatory protein SIRP (OX41) and human SIRPalpha 1. Eur J Immunol 2000, 30:2130–2137.PubMed

21.

van den Nieuwenhof IM, Renardel de Lavalette C, Diaz N, van Die I, van den Berg TK: Differential galactosylation of neuronal and haematopoietic signal regulatory protein-alpha determines its cellular binding-specificity. J Cell Sci 2001, 114:1321–1329.PubMed

22.

Ogura T, Noguchi T, Murai-Takebe R, Hosooka T, Honma N, Kasuga M: Resistance of B16 melanoma cells to CD47-induced negative regulation of motility as a result of aberrant N-glycosylation of SHPS-1. J Biol Chem 2004, 279:13711–13720.CrossRefPubMed

23.

Sarfati M, Fortin G, Raymond M, Susin S: CD47 in the immune response: role of thrombospondin and SIRP-alpha reverse signaling. Curr Drug Targets 2008, 9:842–850.CrossRefPubMed

24.

Ishiwata I, Ishiwata C, Ishiwata E, Sato Y, Kiguchi K, Tachibana T, Hashimoto H, Ishikawa H: Establishment and characterization of a human malignant choroids plexus papilloma cell line (HIBCPP). Hum Cell 2005, 18:67–72.CrossRefPubMed

25.

McGuinness BT, Clarke IN, Lambden PR, Barlow AK, Poolman JT, Jones DM, Heckels JE: Point mutation in meningococcal por A gene associated with increased endemic disease. Lancet 1991, 337:514–517.CrossRefPubMed

26.

Ram S, Cox AD, Wright JC, Vogel U, Getzlaff S, Boden R, Li J, Plested JS, Meri S, Gulati S, Stein DC, Richards JC, Moxon ER, Rice PA: Neisserial lipooligosaccharide is a target for complement component C4b. Inner core phosphoethanolamine residues define C4b linkage specificity. J Biol Chem 2003, 278:50853–50862.CrossRefPubMed

27.

Claus H, Maiden MC, Maag R, Frosch M, Vogel U: Many carried meningococci lack the genes required for capsule synthesis and transport. Microbiology 2002, 148:1813–1819.CrossRefPubMed

28.

Claus H, Maiden MC, Wilson DJ, McCarthy ND, Jolley KA, Urwin R, Hessler F, Frosch M, Vogel U: Genetic analysis of meningococci carried by children and young adults. J Infect Dis 2005, 191:1263–1271.CrossRefPubMed

29.

Knott G, Rosset S, Cantoni M: Focussed ion beam milling and scanning electron microscopy of brain tissue. J Vis Exp 2011, 6:e2588.

30.

Villinger C, Gregorius H, Kranz C, Hohn K, Munzberg C, von Wichert G, Mizaikoff B, Wanner G, Walther P: FIB/SEM tomography with TEM-like resolution for 3D imaging of high-pressure frozen cells. Histochem Cell Biol 2012, 138:549–556.CrossRefPubMed

31.

Staal J, Abramoff MD, Niemeijer M, Viergever MA, van Ginneken B: Ridge-based vessel segmentation in color images of the retina. IEEE Trans Med Imaging 2004, 23:501–509.CrossRefPubMed

32.

Thevenaz P, Ruttimann UE, Unser M: A pyramid approach to subpixel registration based on intensity. IEEE Trans Image Process 1998, 7:27–41.CrossRefPubMed

33.

Abramoff MD, Viergever MA: Computation and visualization of three-dimensional soft tissue motion in the orbit. IEEE Trans Med Imaging 2002, 21:296–304.CrossRefPubMed

34.

Schmid B, Schindelin J, Cardona A, Longair M, Heisenberg M: A high-level 3D visualization API for Java and ImageJ. BMC Bioinforma 2010, 11:274.CrossRef

35.

Zhou J, Stohlman SA, Hinton DR, Marten NW: Neutrophils promote mononuclear cell infiltration during viral-induced encephalitis. J Immunol 2003, 170:3331–3336.CrossRefPubMed

36.

Soehnlein O, Zernecke A, Weber C: Neutrophils launch monocyte extravasation by release of granule proteins. Thromb Haemost 2009, 102:198–205.PubMed

37.

de Vries HE, Hendriks JJ, Honing H, De Lavalette CR, van der Pol SM, Hooijberg E, Dijkstra CD, van den Berg TK: Signal-regulatory protein alpha-CD47 interactions are required for the transmigration of monocytes across cerebral endothelium. J Immunol 2002, 168:5832–5839.CrossRefPubMed

38.

Stefanidakis M, Newton G, Lee WY, Parkos CA, Luscinskas FW: Endothelial CD47 interaction with SIRPgamma is required for human T-cell transendothelial migration under shear flow conditions in vitro. Blood 2008, 112:1280–1289.CrossRefPubMedPubMedCentral

39.

Zen K, Parkos CA: Leukocyte-epithelial interactions. Curr Opin Cell Biol 2003, 15:557–564.CrossRefPubMed

40.

Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L: Neutrophils: molecules, functions and pathophysiological aspects. Lab Invest 2000, 80:617–653.CrossRefPubMed

41.

Edens HA, Levi BP, Jaye DL, Walsh S, Reaves TA, Turner JR, Nusrat A, Parkos CA: Neutrophil transepithelial migration: evidence for sequential, contact-dependent signaling events and enhanced paracellular permeability independent of transjunctional migration. J Immunol 2002, 169:476–486.CrossRefPubMed

42.

Tenenbaum T, Adam R, Eggelnpohler I, Matalon D, Seibt A, GE KN, Galla HJ, Schroten H: Strain-dependent disruption of blood-cerebrospinal fluid barrier by Streptoccocus suis in vitro. FEMS Immunol Med Microbiol 2005, 44:25–34.CrossRefPubMed

43.

Wong D, Prameya R, Dorovini-Zis K: Adhesion and migration of polymorphonuclear leukocytes across human brain microvessel endothelial cells are differentially regulated by endothelial cell adhesion molecules and modulate monolayer permeability. J Neuroimmunol 2007, 184:136–148.CrossRefPubMed

44.

Parkos CA, Delp C, Arnaout MA, Madara JL: Neutrophil migration across a cultured intestinal epithelium. Dependence on a CD11b/CD18-mediated event and enhanced efficiency in physiological direction. J Clin Invest 1991, 88:1605–1612.CrossRefPubMedPubMedCentral

45.

Burns AR, Bowden RA, MacDonell SD, Walker DC, Odebunmi TO, Donnachie EM, Simon SI, Entman ML, Smith CW: Analysis of tight junctions during neutrophil transendothelial migration. J Cell Sci 2000,113(Pt 1):45–57.PubMed

46.

Zen K, Chen CX, Chen YT, Wilton R, Liu Y: Receptor for advanced glycation endproducts mediates neutrophil migration across intestinal epithelium. J Immunol 2007, 178:2483–2490.CrossRefPubMed

47.

Bijuklic K, Jennings P, Kountchev J, Hasslacher J, Aydin S, Sturn D, Pfaller W, Patsch JR, Joannidis M: Migration of leukocytes across an endothelium-epithelium bilayer as a model of renal interstitial inflammation. Am J Physiol Cell Physiol 2007, 293:C486–492.CrossRefPubMed

48.

Rosseau S: Moraxella catarrhalis-Infected Alveolar Epithelium Induced Monocyte Recruitment and Oxidative Burst. Am J Respir Cell Mol Biol 2004, 32:157–166.CrossRefPubMed

49.

Kocabas C, Katsenelson N, Kanswal S, Kennedy MN, Cui X, Blake MS, Segal DM, Akkoyunlu M: Neisseria meningitidis type C capsular polysaccharide inhibits lipooligosaccharide-induced cell activation by binding to CD14. Cell Microbiol 2007, 9:1297–1310.CrossRefPubMed

50.

Soehnlein O, Zernecke A, Eriksson EE, Rothfuchs AG, Pham CT, Herwald H, Bidzhekov K, Rottenberg ME, Weber C, Lindbom L: Neutrophil secretion products pave the way for inflammatory monocytes. Blood 2008, 112:1461–1471.CrossRefPubMedPubMedCentral

51.

Soehnlein O, Lindbom L, Weber C: Mechanisms underlying neutrophil-mediated monocyte recruitment. Blood 2009, 114:4613–4623.CrossRefPubMed

52.

Szmydynger-Chodobska J, Strazielle N, Gandy JR, Keefe TH, Zink BJ, Ghersi-Egea JF, Chodobski A: Posttraumatic invasion of monocytes across the blood-cerebrospinal fluid barrier. J Cereb Blood Flow Metab 2011, 32:93–104.CrossRefPubMedPubMedCentral

53.

Zemans RL, Colgan SP, Downey GP: Transepithelial migration of neutrophils: mechanisms and implications for acute lung injury. Am J Respir Cell Mol Biol 2009, 40:519–535.CrossRefPubMed

54.

van Furth AM, Roord JJ, van Furth R: Roles of proinflammatory and anti-inflammatory cytokines in pathophysiology of bacterial meningitis and effect of adjunctive therapy. Infect Immun 1996, 64:4883–4890.PubMedPubMedCentral

55.

Spanaus KS, Nadal D, Pfister HW, Seebach J, Widmer U, Frei K, Gloor S, Fontana A: C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells in vitro. J Immunol 1997, 158:1956–1964.PubMed

56.

Engelhardt B, Wolburg-Buchholz K, Wolburg H: Involvement of the choroid plexus in central nervous system inflammation. Microsc Res Tech 2001, 52:112–129.CrossRefPubMed

57.

Schwerk C, Adam R, Borkowski J, Schneider H, Klenk M, Zink S, Quednau N, Schmidt N, Stump C, Sagar A, Spellerberg B, Tenenbaum T, Koczan D, Klein-Hitpass L, Schroten H: In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines. Microbes Infect 2011, 13:953–962.CrossRefPubMed

58.

Schluter D, Kaefer N, Hof H, Wiestler OD, Deckert-Schluter M: Expression pattern and cellular origin of cytokines in the normal and Toxoplasma gondii-infected murine brain. Am J Pathol 1997, 150:1021–1035.PubMedPubMedCentral

59.

Netea MG, Simon A, van de Veerdonk F, Kullberg BJ, Van der Meer JW, Joosten LA: IL-1beta processing in host defense: beyond the inflammasomes. PLoS Pathog 2010, 6:e1000661.CrossRefPubMedPubMedCentral

60.

Martinon F, Agostini L, Meylan E, Tschopp J: Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr Biol 2004, 14:1929–1934.CrossRefPubMed

61.

Kanneganti TD, Lamkanfi M, Kim YG, Chen G, Park JH, Franchi L, Vandenabeele P, Nunez G: Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. Immunity 2007, 26:433–443.CrossRefPubMed

62.

Liu Y, Buhring HJ, Zen K, Burst SL, Schnell FJ, Williams IR, Parkos CA: Signal regulatory protein (SIRPalpha), a cellular ligand for CD47, regulates neutrophil transmigration. J Biol Chem 2002, 277:10028–10036.CrossRefPubMed

63.

Liu SQ, Alkema PK, Tieche C, Tefft BJ, Liu DZ, Li YC, Sumpio BE, Caprini JA, Paniagua M: Negative regulation of monocyte adhesion to arterial elastic laminae by signal regulatory protein alpha and Src homology 2 domain-containing protein-tyrosine phosphatase-1. J Biol Chem 2005, 280:39294–39301.CrossRefPubMed

Title: Transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal fluid barrier after bacterial infection in vitro
Authors: Ulrike Steinmann
Julia Borkowski
Hartwig Wolburg
Birgit Schröppel
Peter Findeisen
Christel Weiss
Hiroshi Ishikawa
Christian Schwerk
Horst Schroten
Tobias Tenenbaum
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2013
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-10-31

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Springer Medicine

Transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal fluid barrier after bacterial infection in vitro

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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