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Expression of basic fibroblast growth factor, nerve growth factor, platelet-derived growth factor and transforming growth factor-β in human brain abscess

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Abstract

We correlated the histopathological findings of six human brain abscesses with the expression of basic fibroblast growth factor (bFGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGFβ). The clinical courses ranged from 1 month to 1 year and viridans streptoccus was the major pathogen. In early abscesses, we demonstrated strong bFGF and moderate NGF and PDGF immunoreactivities in neutrophils and monocytes/macrophages infiltrating the abscess wall and in the fibrin layer lining the abscess center. In the subacute cases, growth of capillaries and fibroblasts into the fibrin layer and deposition of collagen resulted in the formation of a mesodermal layer between the abscess center and the outer gliotic layer. The proliferative non-neural cells (endothelial cells, fibroblasts and glial cells) expressed mild to strong bFGF, NGF and PDGF immunoreactivities, while strong TGFβ staining was seen in the extracellular matrix. A loss of growth factor expression and increased fibrosis was seen in the chronic case. These findings suggest that bFGF, NGF, PDGF and TGFβ produced by the continued influx of leukocytes and by the proliferating non-neural cells may mediate various steps of defense mechanisms and wound healing such as angiogenesis, fibrogenesis and gliosis.

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References

  1. Allen RE, Dodson MV, Luiten LS (1984) Regulation of skeletal muscle satellite cell proliferation by bovine pituitary fibroblast growth factor. Exp Cell Res 152: 154–160

    Google Scholar 

  2. Assoian RK, Komoriya A, Meyers CA Miller DM, Sporn MB (1983) Transforming growth factor-beta in human platelets. J Biol Chem 258: 7155–7160

    Google Scholar 

  3. Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB (1987) Expression and secretion of type β transforming growth factor by activated human macrophages. Proc Natl Acad Sci USA 84: 6020–6024

    Google Scholar 

  4. Baird A, Durkin T (1986) Inhibition of endothelial cell proliferation by type-β transforming grwoth factor: interactions with acidic and basic fibroblast growth factor. Biochem Biophy Res Commun 138: 476–482

    Google Scholar 

  5. Bandtlow CE, Heumann R, Schwab ME, Thoenen H (1987) Cellular localization of nerve growth factor by in situ hybridization. EMBO J 6: 891–899

    Google Scholar 

  6. Boyle MDP, Lawman MJP, Gee AP, Young M (1985) Nerve growth factor: a chemotactic factor for polymorphonuclear leukocytes in vivo. J Immunol 135: 564–568

    Google Scholar 

  7. Bracci-Laudiero L, Aloe L, Levi-Montalcini R, Galeazzi M, Schilter D, Scully JL, Otten U (1993) Increased levels of NGF in sera of systemic lupus erythematosus. Neuroreport 4: 563–565

    Google Scholar 

  8. Britt RH, Enzmann DR, Yeager AS (1981) Neuropathological and computerized tomogaphic findings in experimental brain abscess. J Neurosurg 55: 590–603

    Google Scholar 

  9. Broadley KN, Aquino AM, Woodward SC, Buckley-Sturrock A, Sato Y, Rikin DB, Davidson JM (1986) Monospecific antibodies implicate basic fibroblast growth factor in normal wound repair. Lab Invest 61: 571–575

    Google Scholar 

  10. Cancilla PA, Bready J, Berliner J, Sharifi-Nia H, Toga AW, Santori EM, Scully S, de Vellis J (1992) Expression of mRNA for glial fibrillary acidic protein after experimental cerebral injury. J Neuropathol Exp Neurol 51: 560–565

    Google Scholar 

  11. Chen J-K, Hoshi H, McKeehan WL (1987) Transforming growth factor β specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. Proc Natl Acad Sci USA 84: 5287–5291

    Google Scholar 

  12. Cuevas P, Burgos J, Baird A (1988) Basic fibroblast growth factor (FGF) promotes cartilage repair in vivo. Biochem Biophys Res Commun 156: 611–618

    Google Scholar 

  13. Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV (1985) Human transforming growth factor-β complementary DNA sequence and expression in normal and transformed cells. Nature 316: 701–705

    Google Scholar 

  14. Deuel TF (1987) Polypeptide growth factors: role in normal and abnormal cell growth. Annu Rev Cell Biol 3: 443–492

    Google Scholar 

  15. Deuel TF, Senior RM, Huang JS, Griffin GL (1982) Chemotaxis of monocytes and neutrophils to platelet-derived growth factor. J Clin Invest 69: 1046–1049

    Google Scholar 

  16. Finklestein SP, Apostolides PJ, Caday CG, Prosser J, Philips MF, Klagsbrun M (1988) Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds. Brain Res 460: 253–259

    Google Scholar 

  17. Flaris NA, Hickey W (1992) Development and characterization of an experimental model of brain abscess in the rat. Am J Pathol 141: 1299–1307

    Google Scholar 

  18. Folkman J, Klagsbrun N (1987) Angiogenic factors. Science 235: 442–447

    Google Scholar 

  19. Gadient RA, Cron KC, Otten U (1990) Interleukin-1 beta and tumor necrosis factor-alpha synergistically stimulate nerve growth factor (NGF) release from cultured rat astrocytes. Neurosci Lett 117: 335–340

    Google Scholar 

  20. Goedert M, Fine A, Hunt SP, Ullrich A (1988) Nerve growth factor mRNA in peripheral and central rat tissue and in the human central nervous system: lesion effects in the rat brain and levels in Alzheimer's disease. Mol Brain Res 1: 85–92

    Google Scholar 

  21. Gomez-Pinilla F, Lee JW-K, Cotman CW (1992) Basic FGF in adult rat brain: cellular distribution and response to entorhinal lesion and fimbria-fornix transection. J Neurosci 12: 345–355

    Google Scholar 

  22. Gospodarowicz D (1991) Biological activities of fibroblast growth factors. Ann NY Acad Sci 638: 1–8

    Google Scholar 

  23. Heumann R, Korsching S, Bandtlow C, Thoenen H (1987) Changes of nerve growth factor synthesis in nonneural cells in response to sciatic nerve transection. J Cell Biol 104: 1623–1631

    Google Scholar 

  24. Ignotz RA, Endo T, Massague J (1987) Regulation of fibronectin and type 1 collagen mRNA levels by transforming growth factor-beta. J Biol Chem 262: 6443–6446

    Google Scholar 

  25. Klagsbrun M, Sasse J, Sullivan R, Smith JA (1986) Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor. Proc Natl Acad Sci USA 83: 2448–2452

    Google Scholar 

  26. Koroly MJ, Young M (1981) Nerve growth factor. Handb Exp Pharmacol 57: 249–254

    Google Scholar 

  27. Laudiero LB, Aloe L, Levi-Montalcini R, Buttinelli C, Schilter D, Gillessen S, Otten U (1992) Multiple sclerosis patients express increased levels of beta-nerve growth factor in cerebrospinal fluid. Neurosci Lett 147: 9–12

    Google Scholar 

  28. Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237: 1154–1162

    Google Scholar 

  29. Li AKC, Koroly MJ, Schattenkerk ME, Malt A, Young M (1980) Nerve growth factor: acceleration of the rate of wound healing in mice. Proc Natl Acad Sci USA 77: 4379–4382

    Google Scholar 

  30. Liu HM (1978) Axon-sheath cell interaction mediated by a neurotrophic substance. Exp Neurol 66: 123–134

    Google Scholar 

  31. Liu HM (1988) Neovasculature and blood-brain barrier in ischemic brain infarct. Acta Neuropathol (Berl) 75: 422–426

    Google Scholar 

  32. Liu HM, Wang DL, Liu CY (1990) The interaction between endothelial cells with fibrin and collagen during angiogenesis in vivo. In: Liu CY, Chien S (eds) Fibrinogen, thrombosis, coagulation and fibrinolysis. Plenum Press, New York, pp 319–331

    Google Scholar 

  33. Liu HM (1992) The role of extracellular matrix in peripheral nerve regeneration, a wound chamber study. Acta Neuropathol 83: 469–476

    Google Scholar 

  34. Liu HM, Chen HH (1994) Correlation between fibroblast growth factor expression and cell proliferation in experimental brain infarct: studies with proliferating nuclear antigen immunohistochemistry. J Neuropathol Exp Neurol 53: 118–126

    Google Scholar 

  35. Ludwin SK (1985) Reaction of oligodendrocytes and astrocytes to trauma and implantation: a combined autoradiographic and immunohistochemical study. Lab Invest 52: 20–30

    Google Scholar 

  36. Maciag T, Mehman T, Freisel R, Schreiber AB (1984) Heparin binds endothelial cell growth factor, the principle endothelial cell mitogen in bovine brain. Science 225: 932–935

    Google Scholar 

  37. Matsuyama A, Iwata H, Okumura N, Yoshida S, Imaizumi K, Lee Y, Shiraishi S, Shiosaka S (1992) Localization of basic fibroblast growth factor-like immunoreactivity in the rat brain. Brain Res 587: 49–65

    Google Scholar 

  38. Otten U, Ehrhard P, Peck R (1989) Nerve growth factor induces growth and differentiation of human B lymphocytes. Proc Natl Acad Sci USA 86: 10059–10063

    Google Scholar 

  39. Pierce GF (1990) Macrophages: important physiological and pathological sources of polypeptide growth factors. Am J Respir Cell Mol Biol 2: 233–234

    Google Scholar 

  40. Pierce GF, Mustoe TA, Lingelbach J, Masakowski VR, Griffin GL, Senior RM, Deuel TF (1989) Platelet-derived growth factor and transforming growth factor-β enhance tissue repair activities by unique mechanisms. J Cell Biol 109: 429–440

    Google Scholar 

  41. Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH (1987) Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor β J Exp Med 165: 251–256

    Google Scholar 

  42. Raivich G, Kreutzberg GW (1987) Expression of growth factor receptors in injured nervous tissue. 1. Axotomy leads to a shift in the cellular distribution of specific β-nerve growth factor binding in the injured and regenerating PNS. J Neurocytol 16: 689–700

    Google Scholar 

  43. Reier P (1986) Gliosis following CNS injury: the anatomy of astrocytic scars and their influences on axonal elongation. In: Fedoroff S, Vernadakis A (eds) Astrocytes, cell biology and pathology of astrocytes, vol 3. Academic Press, New York, pp 236–324

    Google Scholar 

  44. Roberts AB, Spron MB, Assoian RK, Smith JM, Roche NS, Wakefield ML, Heine UI, Liotta LA, Falanga V, Kehrl JH, Fauci AS (1986) Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 83: 4167–4171

    Google Scholar 

  45. Ross R, Raines EW, Bowen-Pope DF (1986) The biology of platelet-derived growth factor. Cell 46: 155–169

    Google Scholar 

  46. Seppa H, Grotendorst S, Seppa S, Schiffman E, Martin GR (1982) Platelet-derived growth factor is chemotactic for fibroblasts. J Cell Biol 92: 584–588

    Google Scholar 

  47. Walicke PA (1988) Basic and acidic fibroblast growth factors have trophic effects on neurons from multiple CNS regions. J Neurosci 8: 2618–2627

    Google Scholar 

  48. Weller RO, Steart P (1984) Cytology of cerebral abscesses. An immunocytochemical and ultrastructural study. Neuropathol Appl Neurobiol 10: 305–30630

    Google Scholar 

  49. Wheeler EF, Bothwell M (1992) Spatiotemporal pattern of expression of NGF and the low-affinitty NGF receptor in rat embryos suggest functional roles in tissue morphogenesis and myogenesis. J Neurosci 12: 930–945

    Google Scholar 

  50. Yang S (1981) Brain abscesses: a review of 400 cases. J Neurosurg 55: 794–799

    Google Scholar 

  51. Yeh H-J, Ruit KG, Wang Y-X, Parks WC, Snider WD (1991) PDGF-A chain is expressed by mammalian neurons during development and in maturity. Cell 64: 209–216

    Google Scholar 

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Supported by NSC-82-0115-B-006-127 from the National Science Council, Republic of China

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Liu, H.M., Yang, H.B. & Chen, R.M. Expression of basic fibroblast growth factor, nerve growth factor, platelet-derived growth factor and transforming growth factor-β in human brain abscess. Acta Neuropathol 88, 143–150 (1994). https://doi.org/10.1007/BF00294507

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  • DOI: https://doi.org/10.1007/BF00294507

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