GRANULOCYTE-COLONY-STIMULATING FACTOR DOWN-REGULATES ALLOGENEIC IMMUNE-RESPONSES BY POSTTRANSCRIPTIONAL INHIBITION OF TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION

被引:94
作者
KITABAYASHI, A [1 ]
HIROKAWA, M [1 ]
HATANO, Y [1 ]
LEE, M [1 ]
KUROKI, J [1 ]
NIITSU, H [1 ]
MIURA, AB [1 ]
机构
[1] AKITA UNIV,SCH MED,DEPT INTERNAL MED,DIV HEMATOL,AKITA 010,JAPAN
关键词
D O I
10.1182/blood.V86.6.2220.bloodjournal8662220
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We report downregulatory effects of granulocyte colony-stimulating factor (G-CSF) on allogeneic immune responses in vitro. G-CSF did not affect the proliferative response of peripheral blood mononuclear cells (PBMC) against allogeneic Daudi cells but did inhibit tumor necrosis factor (TNF)-alpha secretion. In contrast with G-CSF, granulocyte-macrophage (GM)-CSF and interleukin (IL)-3 enhanced alloactivation-induced TNF-alpha production. G-CSF-mediated suppression of TNF-alpha production was not affected by fixation of stimulators. G-CSF did not inhibit TNF-alpha mRNA expression or accelerate mRNA degradation, whereas pentoxifylline inhibited the expression of TNF-alpha mRNA. These results indicate that G-CSF acts directly on responder cells and modulates TNF-alpha production at posttranscriptional levels. Suppression of TNF-alpha secretion was accompanied by an increase of intracellular cyclic adenosine monophosphate (cAMP) concentration in alloactivated PBMC. The cell permeable cAMP analogue, dibutyryl cAMP, suppressed TNF-alpha secretion without affecting TNF-alpha mRNA expression, G-CSF showed an inhibitory effect on the development of cytotoxic effector cells against allogeneic Daudi cells. Anti-TNF-alpha monoclonal antibody (MoAb) also inhibited the induction of cytolytic activity, and the inhibitory effects of G-CSF and anti-TNF-alpha MoAb on killer activity generation were overcome by adding exogenous TNF-alpha. Hence, impaired generation of cytolytic effector cells by G-CSF is believed to be the result of reduced TNF-alpha production, Collectively, the results described above suggest that G-CSF downregulates allogeneic immune responses by posttranscriptionally inhibiting TNF-alpha production. (C) 1995 by The American Society of Hematology.
引用
收藏
页码:2220 / 2227
页数:8
相关论文
共 44 条
[1]   MARROW TRANSPLANTATION FROM HLA-MATCHED UNRELATED DONORS FOR TREATMENT OF HEMATOLOGIC MALIGNANCIES [J].
BEATTY, PG ;
HANSEN, JA ;
LONGTON, GM ;
THOMAS, ED ;
SANDERS, JE ;
MARTIN, PJ ;
BEARMAN, SI ;
ANASETTI, C ;
PETERSDORF, EW ;
MICKELSON, EM ;
PEPE, MS ;
APPELBAUM, FR ;
BUCKNER, CD ;
CLIFT, RA ;
PETERSEN, FB ;
STEWART, PS ;
STORB, RF ;
SULLIVAN, KM ;
TESLER, MC ;
WITHERSPOON, RP .
TRANSPLANTATION, 1991, 51 (02) :443-447
[2]  
BEGLEY CG, 1988, EXP HEMATOL, V16, P71
[3]  
BIANCO JA, 1991, BLOOD, V78, P1205
[4]  
CHEN ZP, 1992, J BIOL CHEM, V267, P6946
[5]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[6]  
DECKER T, 1988, J IMMUNOL METHODS, V15, P61
[7]  
DEMETRI GD, 1991, BLOOD, V78, P2791
[8]  
GALE RP, 1986, CLIN HAEMATOL, V15, P851
[9]  
GILMAN AG, 1985, CELL, V36, P577
[10]  
GORGEN I, 1992, J IMMUNOL, V149, P918