Abstract
Skin samples from patients with extra-mammary Paget disease, Bowen’s disease, atopic dermatitis, psoriasis and non-lesional skin of nevus pigmentosus were immunohistochemically examined with an anti-soluble erythropoietin receptor antibody (anti-sEPOR antibody), and only the dermal mast cells positively stained in all skin samples were examined. These positively stained dermal cells were proved to be mast cells by double staining with anti-sEPOR antibody and either with anti-bikunin antibody or anti-tryptase antibody. Immunoelectron microscopically these EPOR were found in the secretory granules of the dermal mast cells. Further, EPOR in the mast cells may be consisting of only the extracellular domain of erythropoietin receptor molecule as the mast cells were immunohistochemically not reacted with an antibody to the C-terminal peptide of EPOR. Human mast cell line, HMC-1 cells has immunohistochemically the erythropoietin receptor, which was consisting of a 43 kDa major protein and a 20 kDa minor protein in the immunoelectrophoresis. These data may indicate that EPOR in the mast cells may not be the whole molecule, but probably the soluble one of EPOR.
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Anagnostou A, Liu Z, Steiner M, Chin K, Lee ES, Kessimian N, Noguchi T (1994) Erythropoietin receptor mRNA expression in human endothelial cells. Pro Natl Acad Sci USA 91:3974–3978
Baynes RD, Reddy GK, Shih YJ, Skikne BS, Cook JD (1993) Serum form of the erythropoietin receptor identified by a sequence-specific peptide antibody. Blood 82:2088–2095
Baynes RD (1996) Two serum forms of erythropoietin receptor. Blood 88:3247
Bradding P (1992) Interleukin 4 is located to and released by human mast cells. J Exp Med 176:1381–1386
Buneval P, Sassay C, Mayeux P, Belair MF, Casadevall N, Roux FX, Varet B, Lacombec C (1993) Erythropoietin synthesis by tumor cells in a case of meningioma associated with erythrocytosis. Blood 81:1593–1597
Butterfield JH, Weiler D, Dewald G, Gleich GJ (1988) Establishment of an immature mast cell line from a patient with mast cell leukemia. Leukemic Res 12:345–355
Constantinecu SN, Ghaffari S, Lodish HF (1999) The erythopoietin receptor. Structure, activation and intracellular signal transduction. Trends Endocrinol Metab 10:18–23
Cui CY, Aragane Y, Maeda A, Piao YL, Takahashi M, Kim LH, Tezuka T (1999) Bikunin, a serine protease inhibitor, is present on the cell boundary of epidermis. J Invest Dermatol 113:182–188
Daitou K, Azumi T, Yoshida T, Wataya M (2003) Expression and function of erythropoietin protein in mamma carcinoma. M J Kinki Univ 27:203–213
D’Andrea AD, Lodish HF, Wong GG (1989) Expression cloning of the murine erythropoietin receptor. Cell 57:277–285
Gueston JL, Ternynck T, Avrameras S (1979) The use of Avidin-Biotin interaction in immunoenzymatic techniques. Histochem Cytochem 27:1131–1139
Ide K, Ide H, Itoh H, Yoshida E, Kobayashi T, Tomita M, Maruyama H, Osada Y, Nakahata T, Nawa Y (1999) Immunohistochemical demonstration of inter-alpha-trypsin inhibitor light chain (bikunin) in human mast cells. Cell Tissue Res 297:149–154
Imayama S, Shibata Y, Hori Y (1995) Epidermal mast cells in atopic dermatitis. Lancet 346:1559
Irani AA, Schechter NM, Craig SS, et al. (1986) Two type of human mast cells that have distinct neutral protease compositions. Proc Natl Acad Sci USA 83:4464–4468
Irani AA, Bradford TR, Kepley CL, et al. (1989b) Detection of MCt and MCtc types of human mast cells by immuno-histochemistry using new monoclonal anti-tryptase and anti-chymase antibodies. J Histochem Cytochem 37:1509–1515
Isogai R, Matsukura A, Aragane Y, Maeda A, Matukura M, Yudate T, Sugihara K, Takahasi M, Aisu K, Tezuka T (2002) Quantitative analysis of bikunin-laden mast cells in infantile atopic skin with follicular papules and atopic chronic skin lesions. Arch Dermatol Res 294:387–392
Jarvikallio A, Naukkarinen A, Harvima IT, Aslto ML, Horsmanheimo M (1997) Quantitative analysis of tryptase- and chymase-containing mast cells in atopic dermatitis and nummular eczema. Br J Dermatol 136:871–877
Kusuda S, Cui CY, Takahashi M, Tezuka T (1998) Localization of sphingomyelinase in lesional skin of atopic dermatitis patients. J Invest Dermatol 111:733–738
Lodish HF, Hilton DJ, Klingmuller U, Watowich SS, Wu H (1995) The erythropoietin receptor: iogenesis, dimerization, and intracellular signal transduction. Cold Spring Harb Symp Quant Biol 60:93–104
Masuda S, Nagao M, Takahata K, Konishi Y, Gallyas Jr F, Tabira T, Sasaki R (1993) Functional erythropoietin receptor of the cells with neural characteristics. J Biol Chem 268:11208–11216
Nojchowski DM, Gregory RL, Miller CP, Pandit AK, Pircher TS (1999) Signal transduction in the erythropoietin receptor system. Exp Cell Res 253:143–156
Ogilvie M, Yu X, Nicolas-Metral V, Pulido SM, Liu C, Ruegg UT, Noguchi CT (2000) Erythropoietin stimulates proliferation and interfaces with differentiation of myoblasts. J Biol Chem 275:39754–39761
Sawyer ST, Krantz SB, Sawada K (1989) Receptors for erythropoietin in mouse and human erythroid cells and placenta. Blood 74:103–109
Sugiura H, Uehara M (1993) Mitosis of mast cells in skin lesions of atopic dermatitis. Acta Dermat Venereol 73:296–299
Trimble M, Caro J, Talalla A, Brain M (1991) Secondary erythrocytosis due to a cerebellar hemangioblastoma: demonstation of erythropoietin mRNA in the tumor. Blood 78:599–601
Walsh LJ (1991) Human dermal mast cells contain and release tumor necrosis factor alpha, which includes endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci USA 88:4220–4224
Yoshida S, Bessho M, Sakata K, Hirasawa I, Murayoshi M, Hirashima K (1996) Lack of relationship between soluble EPOR levels and erythroid parameters in anemic patients. Blood 88:3246–3247
Youssoufian H, Longmore G, Neuman D, Yoshimura A, Lodish HF (1993) Structure, function and activation of the erythropoietin receptor. Blood 81:2223–2236
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Isogai, R., Takahashi, M., Aisu, K. et al. The receptor for erythropoietin is present on cutaneous mast cells. Arch Dermatol Res 297, 389–394 (2006). https://doi.org/10.1007/s00403-005-0615-3
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DOI: https://doi.org/10.1007/s00403-005-0615-3