Abstract
The distribution and expression of fetuin, a fetal plasma protein that has been shown to have a wide-spread intracellular presence in many developing tissues including the central nervous system, has been studied in the developing immune and hemopoietic organs of fetal and adult sheep. The presence of fetuin was demonstrated using immuno-cytochemistry and expression of fetuin was studied using northern blot analysis andin situ hybridization. In the developing sheep fetus, fetuin was shown to be expressed first in the hemopoietic cells of the fetal liver and subsequently in the forming spleen. The very first stromal, bone marrow-forming cells, also expressed fetuin mRNA. These cells became more numerous during gestation and by embryonic day (E) 115 (term is 150 days), fetuin-expressing cells were identified morphologically to be monocytes/macrophages. Fetuin protein, on the other hand, was present in all hemopoietic and immune organs from the earliest age studied (E30) but was confined initially to matrix, mesenchymal tissue. Fetuin-positive cells could be identified in the spleen at E60 as early hemopoietic cells, in the lymph nodes at E60 as stromal cells and macrophages, and at E115 in the thymus as macrophages and squamous cells. In the adult, fetuin mRNA was only detectable by northern blot in the liver and the bone marrow. Usingin situ hybridization in adult tissue, fetuin mRNA-positive cells were identified in the bone marrow to be monocytes/macrophages. Additionally, in the spleen germinal centres, fetuin mRNA was identified in cells with the morphology of dendritic cells. Using three separate cellular markers: lysozyme, S-100, and α1-antitrypsin, the cellular identification of fetuin-positive cells was confirmed to be in the monocyte/macrophage lineage.
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References
Adams CW, Poston RN (1990) Macrophage histology in paraffin-embedded multiple sclerosis plaques as demonstrated by the monoclonal pan-macrophage marker HAM-56: correlation with chronicity of the lesion. Acta Neuropathol (Berl) 80: 208–211
Aizawa S, Tavassoli M (1987) In vitro homing of hemopoietic stem cells is mediated by a recognition system with galactosyl and mannaosyl specificities. Proc Natl Acad Sci USA 84: 4485–4489
Brown WM (1991) The plasma protein, fetuin. PhD thesis, University of Southampton, UK
Brown WM, Saunders NR, Møllgård K, Dziegielewski KM (1992a) Fetuin—an old friend revisited. Bioessays 14: 749–755
Brown WM, Dziegielewska KM, Saunders NR, Christie DL, Nawratil P, Müller-Esterl W (1992b) The nucleotide and deduced amino acid structures of sheep and pig fetuin: common structural features of the mammalian fetuin family. Eur J Biochem 205: 321–331
Campbell AD, Long MW, Wicha MS (1987) Hemonectin, a bone marrow adhesion protein specific for cells of granulocyte lineage. Nature 329: 744–746
Chomczynski P, Saachi N (1987) Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159
Dziegielewska KM, Brown WM (1995) Fetuin. RG Landes Co Molecular Biology Intelligence Unit. Springer, Berlin Heidelberg New York, pp 1–178
Dziegielewska KM, Evans CAN, Fossan G, Lorscheider FL, Malinowska DH, Møllgård K, Reynolds ML, Saunders NR, Wilkinson S (1980) Proteins in cerebrospinal fluid and plasma of fetal sheep during development. J Physiol 300: 441–445
Dziegielewska KM, Møllgård K, Reynolds ML, Saunders NR (1987) A fetuin-related glycoprotein (α2HS) in human embryonic and fetal development. Cell Tissue Res 248: 33–41
Dziegielewska KM, Brown WM, Casey S-J, Christie DL, Foreman RC, Hill RM, Saunders NR (1990) The complete cDNA and amino acid sequence of bovine fetuin. Its homology with α2HS glycoprotein and relation to other members of the cystatin superfamily. J Biol Chem 265: 4354–4357
Dziegielewska KM, Reader M, Matthews N, Brown WM, Møllgård K, Saunders NR (1993) Synthesis of the fetal protein fetuin by early developing neurons in the immature cortex. J Neurocytol 22: 266–272
Edgeworth J, Freemont P, Hong N (1989) Ionomycin-regulated phosphorylation of the myeloid calcium-binding protein p14. Nature 342: 189–192
Hayase T, Rice KG, Dziegielewska KM, Kuhlenschmidt M, Reilly T, Lee Y-C (1992) Comparison ofN-glycosides of fetuins from different species and human α2HS glycoprotein. Biochemistry 31: 4915–4921
Morris B, Simpson-Morgan MW (1987) The development of immunological reactivity in fetal lambs. Ann NY Acad Sci 459: 1–13
Pedersen KO (1994) Fetuin, a new globulin isolated from serum. Nature 154: 575
Peters C, O'Shea KS, Campbell AD, Wicha MS, Long MW (1990) Fetal expression of hemonectin: an extracellular matrix hematopoietic cytoadhesion molecule. Blood 75: 357–364
Peters C, Budde CL, Breon TA, Kuper A, Kim J (1995) Ovine bone marrow extracellular matrix and soluble protein extraction: fetuin amino terminus microheterogeneity. Am J Med Sci 309: 285–294
Roitt V, Brostoff J, Male D (1986) Immunology. Gower Medical Publishing, London
Saunders NR, Sheardown SA, Deal A, Møllgård K, Reader M, Dziegielewska KM (1994) Expression and distribution of fetuin in the developing sheep fetus. Histochemistry 102: 457–475
Sullenbarger BA, Petitt MS, Chong P, Long MW, Wicha MS (1995) Murine granulocytic cell adhesion to bone marrow hemonectin is mediated by mannose and galactose. Blood 86: 135–140
Takahashi K, Isobe T, Ohtsuki Y, Sonobe H, Takeda I, Akagi T (1984) Immunocytochemical localization and distribution of S-100 protein in the human lymphoreticular system. Am J Pathol 116: 497–503
Vrati S, Mann DA, Reed KC (1987) Molecular biology reports. Bio-Rad Laboratories 1: 1–4
White H, Totty N, Panayotou G (1993) Hemonectin, a granulocytic cell-binding protein, is related to the plasma glycoprotein fetuin. Eur J Biochem 213: 523–528
Yang F, Chen Z, Bergeron JM, Cupples RL, Friedrichs WE (1992) Human α2HS glycoprotein/bovine fetuin homologue in mice: identification and developmental regulation of the gene. Biochim Biophys Acta 1130: 149–156
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Dziegielewska, K.M., Brown, W.M., Deal, A. et al. The expression of fetuin in the development and maturation of the hemopoietic and immune systems. Histochem Cell Biol 106, 319–330 (1996). https://doi.org/10.1007/BF02473242
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DOI: https://doi.org/10.1007/BF02473242