The polymorphonuclear leukocyte - A new target for erythropoietin

被引:43
作者
Sela, S
Shurtz-Swirski, R
Sharon, R
Manaster, J
Chezar, J
Shkolnik, G
Shapiro, G
Shasha, SM
Merchav, S
Kristal, B [1 ]
机构
[1] Western Galilee Hosp, Nephrol & Hypertens Unit, IL-22100 Nahariyya, Israel
[2] Western Galilee Hosp, Eliachar Res Lab, IL-22100 Nahariyya, Israel
[3] Western Galilee Hosp, Dept Hematol, IL-22100 Nahariyya, Israel
[4] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel
关键词
erythropoietin; erythropoietin receptor; flow cytometry; polymorphonuclear leukocytes; RT-PCR; oxidative stress; inflammation; hemodialysis patients;
D O I
10.1159/000045991
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
A previous study from our laboratory has shown that erythropoietin (EPO), beside its traditional role in erythropoiesis, acts as an alleviator of oxidative stress and inflammation in chronic hemodialysis (HD) patients, conferred in part by activated polymorphonuclear leukocytes (PMNLs), To substantiate this phenomenon, the existence of EPO receptors (EPO-Rs) on PMNL membrane was examined at the transcriptional and translational levels, mRNA for EPO-R was detected in PMNLs using specific primers directed towards the extracellular region of human EPO-R cDNA. The predicted 300-bp fragment was amplified by reverse transcriptase-polymerase chain reaction. Subcloning and sequence analysis revealed 100% homology of this fragment with human EPO-R, The receptor protein was detected on the surface of intact PMNLs using I-125-EpO. Th, protein was further demonstrated by flow cytometric analysis using a fluorescent monoclonal anti-EPO-R. The percentage of PMNLs expressing EPO-R showed a strong correlation with the level of EPO in the serum, suggesting an upregulation of the receptor by the hormone. Taken together with our recent findings that EPO attenuates the oxidative stress and inflammation contributed by PMNLs in HD patients, the detection of functional EPO-R expression in PMNLs places these cells among the nonerythroid, EPO-responsive target populations. Copyright (C) 2001 S. Karger AG. Basel.
引用
收藏
页码:205 / 210
页数:6
相关论文
共 30 条
[2]   ERYTHROPOIETIN RECEPTOR MESSENGER-RNA EXPRESSION IN HUMAN ENDOTHELIAL-CELLS [J].
ANAGNOSTOU, A ;
LIU, ZY ;
STEINER, M ;
CHIN, K ;
LEE, ES ;
KESSIMIAN, N ;
NOGUCHI, CT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) :3974-3978
[3]  
BROUDY VC, 1990, BLOOD, V75, P1622
[4]   ERYTHROPOIETIN RECEPTOR - SUBUNIT STRUCTURE AND ACTIVATION [J].
DANDREA, AD ;
ZON, LI .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (03) :681-687
[5]   EXPRESSION CLONING OF THE MURINE ERYTHROPOIETIN RECEPTOR [J].
DANDREA, AD ;
LODISH, HF ;
WONG, GG .
CELL, 1989, 57 (02) :277-285
[6]   LOCALIZATION OF SPECIFIC ERYTHROPOIETIN BINDING-SITES IN DEFINED AREAS OF THE MOUSE-BRAIN [J].
DIGICAYLIOGLU, M ;
BICHET, S ;
MARTI, HH ;
WENGER, RH ;
RIVAS, LA ;
BAUER, C ;
GASSMANN, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (09) :3717-3720
[7]   CORRECTION OF THE ANEMIA OF END-STAGE RENAL-DISEASE WITH RECOMBINANT-HUMAN-ERYTHROPOIETIN - RESULTS OF A COMBINED PHASE-I AND PHASE-II CLINICAL-TRIAL [J].
ESCHBACH, JW ;
EGRIE, JC ;
DOWNING, MR ;
BROWNE, JK ;
ADAMSON, JW .
NEW ENGLAND JOURNAL OF MEDICINE, 1987, 316 (02) :73-78
[8]  
FRASER JK, 1988, EXP HEMATOL, V16, P836
[9]   Erythropoietin upregulates the expression of its own receptor in TF-1 cell line [J].
Grossi, A ;
Vannucchi, AM ;
Bacci, P ;
Caporale, R ;
Cappelli, G ;
Visconti, G ;
Pagliai, G ;
Ferrini, PR .
LEUKEMIA RESEARCH, 1998, 22 (02) :145-151
[10]  
JONES SS, 1990, BLOOD, V76, P31