We performed an immunohistochemical study on 5 normal marrow samples and 3 fibrotic marrow samples to investigate the cellular distribution of various isoforms of platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), basic fibroblast growth factor (bFGF), and their corresponding receptors. Immature hematopoietic precursors strongly expressed PDGF-B, all the TGF-β isoforms, PDGFRβ, TGFβRI and II, and FGFR1, 3, and 4. Megakaryocytes stained primarily for PDGF-B, TGF-β2–3, and PDGFRβ. Histiocytes displayed intense TGF-β1, bFGF, and FGFR2 expression. Fibroblasts and endothelial cells carried receptors for all the aforementioned cytokines. The last 2 cell types also expressed the ligand cytokines to varied degrees.

Reilly JT: Idiopathic myelofibrosis: Pathogenesis, natural history and management. Blood Rev 1997;11:233–242.
Siegbahn A, Hammacher A, Westermark B, Heldin CH: Differential effects of the various isoforms of platelet-derived growth factor on chemotaxis of fibroblasts, monocytes, and granulocytes. J Clin Invest 1990;85:916–920.
Kimura A, Katoh O, Kuramoto A: Effects of platelet derived growth factor, epidermal growth factor and transforming growth factor-beta on the growth of human marrow fibroblasts. Br J Haematol 1988;69:9–12.
Bonner JC, Osornio-Vargas AR, Badgett A, Brody AR: Differential proliferation of rat lung fibroblasts induced by the platelet-derived growth factor-AA, -AB, and -BB isoforms secreted by rat alveolar macrophages. Am J Respir Cell Mol Biol 1991;5:539–547.
Osornio-Vargas AR, Goodell AL, Hernandez-Roderiguez NA, Brody AR, Coin PG, Badgett A, Bonner JC: Platelet-derived growth factor (PDGF)-AA, -AB, and -BB induce differential chemotaxis of early-passage rat lung fibroblasts in vitro. Am J Respir Cell Mol Biol 1995;12:33–40.
Heldin CH, Westermark B: Platelet-derived growth factor: Mechanism of action and possible in vivo function. Cell Regul 1990;1:555–566.
Fava RA, Casey TT, Wilcox J, Pelton RW, Moses HL, Nanney LB: Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules. Blood 1990;76:1946–1955.
Kimura A, Katoh O, Hyodo H, Kuramoto A: Transforming growth factor-beta regulates growth as well as collagen and fibronectin synthesis of human marrow fibroblasts. Br J Haematol 1989;72:486–491.
Massague J: The transforming growth factor-beta family. Annu Rev Cell Biol 1990;6:597–641.
Shah M, Foreman DM, Ferguson MW: Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring. J Cell Sci 1995;108:985–1002.
Lopez-Casillas F, Wrana JL, Massague J: Betaglycan presents ligand to the TGF beta signaling receptor. Cell 1993;73:1435–1444.
Wrana JL, Attisano L, Wieser R, Ventura F, Massague J: Mechanism of activation of the TGF-beta receptor. Nature 1994;370:341–347.
Lin HY, Wang XF, Ng-Eaton E, Weinberg RA, Lodish HF: Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase. Cell 1992;68:775–785.
Ratajczak MZ: Fibroblast growth factors and early hemopoietic cell development. Leuk Lymphoma 1997;27:221–229.
Brunner G, Nguyen H, Gabrilove J, Rifkin DB, Wilson EL: Basic fibroblast growth factor expression in human bone marrow and peripheral blood cells. Blood 1993;81:631–638.
Gospodarowicz D, Ferrara N, Schweigerer L, Neufeld G: Structural characterization and biological functions of fibroblast growth factor. Endocr Rev 1987;8:95–114.
Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M: Receptor specificity of the fibroblast growth factor family. J Biol Chem 1996;271:15292–15297.
Bikfalvi A, Han ZC: Angiogenic factors are hematopoietic growth factors and vice versa. Leukemia 1994;8:523–529.
Battegay EJ: Angiogenesis: Mechanistic insights, neovascular diseases, and therapeutic prospects. J Mol Med 1995;73:333–346.
Hino M, Tojo A, Miyazono K, Urabe A, Takaku F: Effects of type beta transforming growth factors on hematopoietic progenitor cells. Br J Haematol 1988;70:143–147.
Allouche M: Basic fibroblast growth factor and hematopoiesis. Leukemia 1995;9:937–942.
Yanagida M, Ide Y, Imai A, Toriyama M, Aoki T, Harada K, Izumi H, Uzumaki H, Kusaka M, Tokiwa T: The role of transforming growth factor-beta in PEG-rHuMGDF-induced reversible myelofibrosis in rats. Br J Haematol 1997;99:739–745.
Yan XQ, Lacey D, Hill D, Chen Y, Fletcher F, Hawley RG, McNiece IK: A model of myelofibrosis and osteosclerosis in mice induced by overexpressing thrombopoietin (mpl ligand): Reversal of disease by bone marrow transplantation. Blood 1996;88:402–409.
Castro-Malaspina H, Rabellino EM, Yen A, Nachman RL, Moore MA: Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts. Blood 1981;57:781–787.
Schmitz B, Thiele J, Kaufmann R, Witte O, Wickenhauser C, Kuhn-Regnier F, Fischer R: Megakaryocytes and fibroblasts – interactions as determined in normal human bone marrow specimens. Leuk Res 1995;19:629–637.
Martyre MC, Magdelenat H, Bryckaert MC, Laine-Bidron C, Calvo F: Increased intraplatelet levels of platelet-derived growth factor and transforming growth factor-beta in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 1991;77:80–86.
Martyre MC, Le Bousse-Kerdiles MC, Romquin N, Chevillard S, Praloran V, Demory JL, Dupriez B: Elevated levels of basic fibroblast growth factor in megakaryocytes and platelets from patients with idiopathic myelofibrosis. Br J Haematol 1997;97:441–448.
Dalley A, Smith JM, Reilly JT, Neil SM: Investigation of calmodulin and basic fibroblast growth factor (bFGF) in idiopathic myelofibrosis: Evidence for a role of extracellular calmodulin in fibroblast proliferation. Br J Haematol 1996;93:856–862.
Rameshwar P, Chang VT, Thacker UF, Gascon P: Systemic transforming growth factor-beta in patients with bone marrow fibrosis – pathophysiological implications. Am J Hematol 1998;59:133–142.
Le Bousse-Kerdiles MC, Chevillard S, Charpentier A, Romquin N, Clay D, Smadja-Jaffe F, Praloran V, Dupriez B, Demory JL, Jasmin C, Martyre MC: Differential expression of transforming growth factor-beta, basic fibroblast growth factor, and their receptors in CD34+ hematopoietic progenitor cells from patients with myelofibrosis and myeloid metaplasia. Blood 1996;88:4534–4546.
Zauli G, Visani G, Catani L, Vianelli N, Gugliotta L, Capitani S: Reduced responsiveness of bone marrow megakaryocyte progenitors to platelet-derived transforming growth factor beta 1, produced in normal amount in patients with essential thrombocythaemia. Br J Haematol 1993;83:14–20.
Rougier F, Dupuis F, Denizot Y: Human bone marrow fibroblast – an overview of their characterization, proliferation and inflammatory mediator production. Hematol Cell Ther 1996;38:241–246.
Keutzer JC, Sytkowski AJ: Regulated production of a pleiotropic cytokine-platelet-derived growth factor – by differentiating erythroid cells in vitro and in vivo. Proc Natl Acad Sci USA 1995;92:4967–4971.
Yang M, Chesterman CN, Chong BH: Recombinant PDGF enhances megakaryocytopoiesis in vitro. Br J Haematol 1995;91:285–289.
Bonnet D, Lemoine FM, Najman A, Guigon M: Comparison of the inhibitory effect of AcSDKP, TNF-alpha, TGF-beta, and MIP-1 alpha on marrow-purified CD34+ progenitors. Exp Hematol 1995;23:551–556.
Sytkowski AJ, O’Hara C, Vanasse G, Armstrong MJ, Kreczko S, Dainiak N: Characterization of biologically active, platelet-derived growth factor-like molecules produced by murine erythroid cells in vitro and in vivo. J Clin Invest 1990;85:40–46.
Dainiak N, Davies G, Kalmanti M, Lawler J, Kulkarni V: Platelet-derived growth factor promotes proliferation of erythropoietic progenitor cells in vitro. J Clin Invest 1983;71:1206–1214.
Delwiche F, Raines E, Powell J, Ross R, Adamson J: Platelet-derived growth factor enhances in vitro erythropoiesis via stimulation of mesenchymal cells. J Clin Invest 1985;76:137–142.
Tefferi A: Pathogenetic mechanisms in chronic myeloproliferative disorders: Polycythemia vera, essential thrombocythemia, agnogenic myeloid metaplasia, and chronic myelogenous leukemia. Semin Hematol 1999;36(suppl 2): 3–8.
Johnston JB, Dalal BI, Israels SJ, Oh S, McMillan E, Begleiter A, Michaud G, Israels LG, Greenberg AH: Deposition of transforming growth factor-beta in the marrow in myelofibrosis, and the intracellular localization and secretion of TGF-beta by leukemic cells. Am J Clin Pathol 1995;103:574–582.
Hammacher A, Hellman U, Johnsson A, Ostman A, Gunnarsson K, Westermark B, Wasteson A, Heldin CH: A major part of platelet-derived growth factor purified from human platelets is a heterodimer of one A and one B chain. J Biol Chem 1988;263:16493–16498.
Katoh O, Kimura A, Itoh T, Kuramoto A: Platelet derived growth factor messenger RNA is increased in bone marrow megakaryocytes in patients with myeloproliferative disorders. Am J Hematol 1990;35:145–150.
Gladwin AM, Carrier MJ, Beesley JE, Lelchuk R, Hancock V, Martin JF: Identification of mRNA for PDGF B-chain in human megakaryocytes isolated using a novel immunomagnetic separation method. Br J Haematol 1990;76:333–339.
Sariban E, Kufe D: Expression of the platelet-derived growth factor 1 and 2 genes in human myeloid cell lines and monocytes. Cancer Res 1988;48:4498–4502.
Malden LT, Chait A, Raines EW, Ross R: The influence of oxidatively modified low density lipoproteins on expression of platelet-derived growth factor by human monocyte-derived macrophages. J Biol Chem 1991;266:13901–13907.
Ross R, Masuda J, Raines EW, Gown AM, Katsuda S, Sasaharan M, Malden LT, Masuko H, Sato H: Localization of PDGF-B protein in macrophages in all phases of atherogenesis. Science 1990;248:1009–1012.
Kimura A, Nakata Y, Hyodo H, Kuramoto A, Satow Y: Platelet-derived growth factor expression in accelerated and blastic phase of chronic myelogenous leukaemia with myelofibrosis. Br J Haematol 1994;86:303–307.
Collins T, Ginsburg D, Boss JM, Orkin SH, Pober JS: Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. Nature 1985;316:748–750.
Coker RK, Laurent GJ, Shahzeidi S, Lympany PA, du Bois RM, Jeffery PK, McAnulty RJ: Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis. Am J Pathol 1997;150:981–991.
Graycar JL, Miller DA, Arrick BA, Lyons RM, Moses HL, Derynck R: Human transforming growth factor-beta 3: Recombinant expression, purification, and biological activities in comparison with transforming growth factors-beta 1 and -beta 2. Mol Endocrinol 1989;3:1977–1986.
Ellis IR, Schor SL: Differential motogenic and biosynthetic response of fetal and adult skin fibroblasts to TGF-beta isoforms. Cytokine 1998;10:281–289.
Thiele J, Braeckel C, Wagner S, Falini B, Dienemann D, Stein H, Fischer R: Macrophages in normal human bone marrow and in chronic myeloproliferative disorders: An immunohistochemical and morphometric study by a new monoclonal antibody (PG-M1) on trephine biopsies. Virchows Arch A Pathol Anat Histopathol 1992;421:33–39.
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