Abstract
CD43 (also known as leukosialin and sialophorin) is a surface sialoglycoprotein expressed at high levels on most leukocytes implicated in adhesion, antiadhesion, and activation/proliferation mechanisms. We studied the expression of this molecule on the leukocytes of patients with myelodysplastic syndromes (MDSs) in an effort to detect acquired deficiencies of this molecule. We used immunofluorescence flow cytometry in analyzing whole blood and isolated neutrophils from 49 MDS patients, 33 men and 16 women aged 33 to 85 years (median, 75 years), and 18 healthy individuals aged 35 to 80 years (median, 72 years). According to French-American-British classification criteria, 13 patients had refractory anemia, 18 had refractory anemia with ringed sideroblasts, 9 had refractory anemia with excess of blasts, 4 had refractory anemia with excess of blasts in transformation to acute leukemia, and 5 had chronic myelomonocytic leukemia. We found decreased expression of CD43 on the neutrophils of these patients, and we correlated this finding with the activation status of these cells as it is defined by their pheno-types. We studied the expression of CD11b, CD18, CD35, CD67, CD69, CD44, and CD53 molecules known to be changed in the activated form of neutrophils. CD43 expression correlated positively with CD53 and CD44 expression and negatively with CD11b, CD18, CD35, CD67, and CD69 expression. Additionally, increased levels of soluble vascular cell adhesion molecules were detected in these patients, suggesting endothelial cell activation. In conclusion, we believe that the decreased expression of CD43 on the neutrophils of MDS patients is associated with activation of these cells and is probably due to cleavage of the molecule from the cell surface and that the same mechanism is possibly responsible for the parallel down-regulation of CD44 and CD53.
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Zannetino CWA, Buhring H-J, Niutta S, Watt MS, Benton MA, Simmons PJ. The sialomucin 164, an adhesive glycoprotein expressed by human hemopoietic progenitors and bone marrow stromal cells that serves as a potent negative regulator of hemo-poiesis.Blood. 1998;92:2613–2628.
Verfaillie CM. Adhesion receptors as regulators of the hemopoietic process.Blood. 1998;92:2609–2612.
Rieu P, Porteu F, Bessou G, Lesavre P, Halbwachs-Mecarelli L. Human neutrophils release their major membrane sialoprotein, leukosialin (CD43), during cell activation.Eur J Immunol. 1992;22:3021–3026.
Moore T, Huang S, Terstappen LW, Bennett M, Kumar V. Expression of CD43 on murine and human pluripotent haematopoietic stem cells.J Immunol. 1994;153:4978–4987.
Fukuda M. Leukosialin, a major O-glycan-containing sialoglyco-protein defining leukocyte differentiation and malignancy.Glyco-biology. 1991;1:347–56.
Misawa Y, Nagaoka H, Kimoto H, et al. CD43 expression in a B cell lymphoma, WEHI 231, reduces susceptibility to G1 arrest and extends survival in culture upon serum depletion.Eur J Immunol. 1996;26:2573–2581.
Ostberg JR, Barth RK, Frelinger JG. The Roman god Janus: a paradigm for the function of CD43.Immunol Today. 1998;19:546–550.
NongYH, Remold-O’Donnell E, LeBien TW, Remold HG. A monoclonal antibody to sialophorin (CD43) induces homotypic adhesion and activation of human monocytes.J Exp Med. 1989;170:259–267.
Piller F, Piller V, Fox RI, Fukuda M. Human T lymphocyte activation is associated with changes in O-glycan biosynthesis.J Biol Chem. 1988;263:15146–15150.
Campanero MR, Pulido R, Alouso JL, et al. Downregulation by tumor necrosis factor-alpha of neutrophil cell surface expression of the sialophorin CD43 and the hyaluronate receptor CD44 through a proteolytic mechanism.Eur J Immunol. 1991;21:3045–3048.
Basil V, Strominger JL. CD43, the major sialoglycoprotein of human leukocytes is proteolytically cleaved from the surface of stimulated lymphocytes and granulocytes.Proc Natl Acad Sci U S A. 1993;90:3792–3796.
Remold-O’Donnell E, Parent D: Two proteolytic pathways for down-regulation of the barrier molecule CD43 of human neutrophils.J Immunol. 1994;152:3595–3605.
Giordanengo V, Limouse M, Peyron J-F, Lefebvre J-C. Lympho-cytic CD43 and CD45 bear sulphate residues potentially implicated in cell-cell interactions.Eur J Immunol. 1995;25:274–278.
Silverman LB, Wong CK, Remold-O’Donnell E, et al. Mechanism of mononuclear cell activation by an anti-CD43 agonistic antibody.J Immunol. 1990;142:4194–4200.
Dorfman KS, Litaker W, Baecher CM, Frelinger JG. The nucleotide sequence of Ly48: the mouse homologue of CD43.Nucl Acid Res. 1990;18:4932.
Pallant A, Eskenazi A, Mattei MG, et al. Characterization ofcDNA encoding human leukosialin and localization of the leukosialin gene to chromosome 16.Proc Natl Acad Sci U S A. 1989;86:1328–1332.
Manjunath N, Ardman B. CD43 regulates tyrosine kinase phos-phorylation of a 93 kDa protein in T lymphocytes.Blood. 1995;86:4194–4198.
Manjunath N, Johnson RS, Staunton DE, Pasqualini R, Ardman B. Targeted disruption of CD43 genes enhances T lymphocyte adhesion.J Immunol. 1993;151:1528–1534.
Manjunath N, Correa M, Ardman M, Ardman B. Negative regulation of T-cell adhesion and activation by CD43.Nature. 1995;377:535–538.
Park JK, Rosenstein YJ, Remold-O’Donnell E, Bierer BE, Rosen FS, Burakoff SJ. Enhancement of T-cell activation by the CD43 molecule whose expression is defective in Wiscott-Aldrich syndrome.Nature. 1991;350:706–709.
Mentzer SJ, Remold-O’Donnell E, Crimmins MAV, Bierer BE, Rosen FS, Burakoff SJ. Sialophorin, a surface sialoglycoprotein defective in the Wiscott-Aldrich syndrome is involved in human T lymphocyte proliferation.J Exp Med. 1987;165:1383–1392.
Vargas-Cortes M, Axelson B, Larsson A, Berzins T, Perlman P. Enhancement of human spontaneous cell-mediated cytotoxicity by a monoclonal antibody against the large sialoglycoprotein (CD43) on peripheral blood lymphocytes.Scand J Immunol. 1988;27:661–671.
Axelson B, Youseffi-Etemad R, Hammarstrom S, Perlman P. Induction of aggregation and enhancement of proliferation and IL-2 secretion in human T-cells by antibodies to CD43.J Immunol. 1988;141:2912–2917.
Ardman B, Sikorski M, Staunton D. CD43 interferes with T-lymphocyte adhesion.Proc Natl Acad Sci U S A. 1992;89:5001–5005.
Dragone LL, Barth RK, Sitar KL, Disbrow GL, Frelinger JG. Disregulation of leukosialin (CD43, Ly48, sialophorin) expression in the B-cell lineage of transgenic mice increases splenic B-cell number and survival.Proc Natl Acad Sci U S A. 1995;92:626–630.
Kudo S. Methyl-CpG-binding protein MeCP2 represses Sp1-activated transcription of the human leukosialin gene when the promoter is methylated.Mol Cell Biol. 1998;18:5492–5499.
Lesley GE, Tao W, Fellinger W, The H-S, Ziltener JH. The CD43 130 kDa peripheral T-cell activation antigen is downregulated in thymic positive selection.Blood. 1996;88:1725–1732.
Remold-O’Donnell E, Kenney DM, Parkman R, Cairns L, Savage B, Rosen SF. Characterization of a human lymphocyte surface sialoglycoprotein that is defective in Wiscott-Aldrich syndrome.J Exp Med. 1984;159:1705–1723.
Ostberg RJ, Dragone LL, Driskel T, et al. Disregulated expression of CD43 (leukosialin, sialophorin) in the B cell lineage leads to immunodeficiency.J Immunol. 1996;157:4876–4884.
Ardman B, Sikorski MA, Settles M, Staunton DE. Human immunodeficiency virus type 1-infected individuals make autoantibodies that bind to CD43 on the normal thymic lymphocytes.J Exp Med. 1990;172:1151–1158.
Abramson JS, Hudnor HR. Role of the sialophorin (CD43) receptor in mediating influenza A virus-induced polymorphonuclear leukocytes disjunction.Blood. 1995;85:1615–1619.
Hartshorn KL, Liou SL, White MR, Kazhdan MM, Tauber JL, Tauber AI. Neutrophil activation by influenza A virus: role of hemaglutinine binding to specific sialic acid-bearing cellular proteins.J Immunol. 1995;54:3952–3960.
Rothwell SW, Wright DG. Characterization of influenza A virus binding sites on human neutrophils.J Immunol. 1994;152:2358–2367.
Ostberg JR, Dragone LL, Waugh R, Ryan D, Frelinger JG, Barth RK. Disregulated expression of leukosialin (CD43) in the erythroid lineage of transgenic mice results in microcytosis.Transgenics. 1996;2:41.
Basil V, Brandt JE, Hoffman R. Resistance of human hemopoietic stem cells to a monoclonal antibody recognizing CD43.Stem Cell. 1997;15(suppl 1):13–19.
Basil V, Brandt J, Tsukamoto A, Hoffman R. Apoptosis of human hematopoietic progenitor cells induced by crosslinking surface CD43, the major sialoglycoprotein of leukocytes.Blood. 1995;86:502–511.
Bazil V, Brandt J, Chen S, et al. A monoclonal antibody recognizing CD43 (leukosialin) initiates apoptosis of human hemopoietic progenitor cells but not stem cells.Blood. 1996;87:1272–1281.
Stockl J, Majdic O, Kohl P, Pickl FW, Menzel J, Knapp W. Leukosialin (CD43)-major histocompatibility class I molecule interactions involved in spontaneous T cell conjugate formation.J Exp Med. 1996;184:1769–1779.
Fanales-Belasio E, Zambruno G, Cavani A, Girolomoni G. Antibodies against sialophorin (CD43) enhance the capacity of dendritic cells to activate T lymphocytes.J Immunol. 1997;159:2203–2211.
Woodman RL, Johnston B, Hickey MJ, et al. The functional paradox of CD43 in leukocyte recruitment: a study using CD43-deficient mice.J Exp Med. 1998;188:2181–2186.
Lopez S, Seveau S, Lesavre P, Robinson MK, Halbwachs-Mecarelli L. CD43 shedding is an initial event during neutrophil migration, which could be closely related to the spreading of adherent cells.Cell Adhes Commun. 1998;5:151–160.
Bennett J, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes.Br J Haematol. 1982;51:189–199.
Felzmann T, Gisslinger H, Krieger O, Majdic O, Ludwig H, Koller U. Immunophenotypic characterization of myelomonocytic cells in patients with myelodysplastic syndrome.Br J Haematol. 1993;84:428–435.
Kyriakou D, Papadaki H, Sakelariou D, Eliopoulos AG, Kapsimali V, Eliopoulos GD. Flow cytometric analysis of peripheral blood lymphocytes in patients with chronic idiopathic neutropenia of adults.Ann Hematol. 1997;75:103–110.
Babina M, Weber S, Henz B. CD43 (leukosialin, sialophorin) expression is differentially regulated by retinoic acids.Eur J Immunol. 1997;27:1147–1151.
Kyriakou D, Papadaki H, Katrinakis G, Eliopoulos AG, Eliopoulos GD. Serum soluble IL-6 receptor concentration correlate with stages of multiple myeloma defined by serum b2-microglobulin and c-reactive protein.Int J Hematol. 1997;66:367–371.
Felzmann T, Gadd S, Majdic O, et al. Analysis of function-associated receptor molecules on peripheral blood and synovial fluid granulocytes from patients with rheumatoid and reactive arthritis.J Clin Immunol. 1991;11:205–212.
Mazzone A, Ricevuti G, Pasoti D, et al. The CD11/CD18 granulocyte adhesion molecules in myelodysplastic syndromes.Br J Haematol. 1993;83:245–252.
Hastl R, Nilson I, Widell S, Ost A. Diagnostic significance of dysplastic features of peripheral blood polymorphs in myelodysplastic syndromes.Leuk Res. 1998;13:173–178.
Hernandez-Garcia C, Fernandez-Gutierez B, Morado IC, Banares AA, Jover JA. The CD69 activation pathway in rheumatoid arthritis synovial fluid T cells.Arthr Reum. 1996;39:1277–1286.
Tassone P, Turco MC, Tuccillo F, et al. CD69 expression on primitive progenitor cells and hematopoietic malignancies.Tissue Antigens. 1996;48:65–68.
Castellanos MC, Munoz C, Montoya MC, Lara-Pezi E, Lopez-Cabrera M, de Landazuri MO. Expression of the leukocyte early activation antigen CD69 is regulated by the transcription factor AP-1.J Immunol. 1997;159:5463–5473.
Fisher GF, Majdic O, Gadd S, Knapp W. Signal transduction in lym-phocytic and myeloid cells via CD24, a new member of phosphoinositol-anchored membrane molecules.J Immunol. 1990;144:638–641.
Ross GD, Medoff ME. Membrane receptors specific for bound fragments of C3.Adv Immunol. 1985;37:217–235.
Arnaout MA, Spits H, Terhorst C, Pitt J, Todd RF. Deficiency of leukocyte surface glycoprotein (LFA-1) in two patients with Mo-1 deficiency.J Clin Invest. 1984;74:11291–11296.
Kyriakou DS, Alexandrakis M, Tzardi M, Stephanaki K, Eliopoulos GD. Downregulation of CD43 in RAEB and RAEB-t patients: report of three cases.Am J Hematol. 2000;63:20–27.
Arnaout MA. Structure and function of the leukocyte adhesion molecules CD11/CD18.Blood. 1990;75:1037–1045.
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Kyriakou, D., Alexandrakis, M.G., Kyriakou, E.S. et al. Reduced CD43 Expression on the Neutrophils of MDS Patients Correlates With an Activated Phenotype of These Cells. Int J Hematol 73, 483–491 (2001). https://doi.org/10.1007/BF02994011
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DOI: https://doi.org/10.1007/BF02994011