THE POTENTIAL ROLE OF THE MACROPHAGE-COLONY-STIMULATING FACTOR, CSF-1, IN INFLAMMATORY RESPONSES - CHARACTERIZATION OF MACROPHAGE CYTOKINE GENE-EXPRESSION

被引:32
作者
EVANS, R
KAMDAR, SJ
FULLER, JA
KRUPKE, DM
机构
[1] The Jackson Laboratory, Bar Harbor, ME 04609
关键词
MONONUCLEAR PHAGOCYTES; SERUM CONCENTRATION; B6.SCID/SCID AND NOD.SCID/SCID MICE; CSF-1; RECEPTOR;
D O I
10.1002/jlb.58.1.99
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In this report we report that recombinant human monocyte-macrophage colony-stimulating factor-1 (CSF-1) induces resident murine peritoneal cells (PCs) to transcribe several inflammatory cytokine genes, including interleukin (IL)-1 alpha, IL-1 beta, IL-6, and granulocyte-macrophage CSF in a dose-dependent and time-related manner, Peak mRNA levels were seen between 4 and 6 h, CSF-1 did not modulate the expression of tumor necrosis factor-alpha mRNA. The serum content of the culture medium appeared to regulate both the extent of CSF-1-induced gene transcription and the adherence properties of the cells, Decreasing the serum concentration significantly reduced CSF-1-induced transcription and was associated with the rapid spreading of the majority of the adherent cells, This reduced sensitivity to CSF-1 was paralleled by a markedly lower levels of c-fms mRNA encoding the CSF-1 receptor, Induced gene transcription was followed by the release of large quantities of Il-6 only. IL-1 activity remained associated with the cells, Neither supernatant nor cell lysate granulocyte-macrophage CSF activity was inducible above the low levels associated with control cultures, Evidence that the mononuclear phagocytes, as opposed to B or T cells, were the targets of CSF-1 was obtained in two ways: (1) PCs from B6 scid/scid and NOD scid/scid mice consisting of 78-86% MAC-1(+), F4/80(+) cells and few B or T cells, as shown by flow cytometry analysis, released 5- to 10-fold more IL-6 in response to CSF-1 stimulation than B6 PCs, which contained =30% double-positive cells, and (2) pretreatment of B6 PCs with antibodies to the CSF-1 receptor blocked the CSF-1-induced secretion of IL-6. These data suggest that CSF-1 primes noninflammatory mononuclear phagocytes for a role in inflammatory responses but does not provide the necessary signals for either secretion or translation of all cytokines equally.
引用
收藏
页码:99 / 107
页数:9
相关论文
共 40 条
[1]  
ACERCI RJ, 1989, P NATL ACAD SCI USA, V86, P8818
[2]  
BAKER AH, 1993, ONCOGENE, V8, P371
[3]  
BAKOUCHE O, 1992, J IMMUNOL, V148, P84
[4]  
BEN D, 1993, EXP HEMATOL, V21, P623
[5]   REGULATION OF SYSTEMIC MACROPHAGE IL-1 GENE-TRANSCRIPTION - THE INVOLVEMENT OF TUMOR-DERIVED MACROPHAGE GROWTH-FACTOR, CSF-1 [J].
EVANS, R ;
DUFFY, TM ;
BLAKE, SS ;
LIN, HS .
JOURNAL OF LEUKOCYTE BIOLOGY, 1989, 46 (05) :428-433
[6]  
EVANS R, 1993, J IMMUNOL, V150, P177
[7]   SYNERGISTIC INTERACTION OF BACTERIAL LIPOPOLYSACCHARIDE AND THE MONOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR - POTENTIAL QUANTITATIVE AND QUALITATIVE CHANGES IN MACROPHAGE-PRODUCED CYTOKINE BIOACTIVITY [J].
EVANS, R ;
KAMDAR, SJ ;
DUFFY, TM ;
FULLER, J .
JOURNAL OF LEUKOCYTE BIOLOGY, 1992, 51 (01) :93-96
[8]  
EVANS R, 1991, J LEUKOCYTE BIOL, V580, P317
[9]  
FIBBE WE, 1989, EXP HEMATOL, V17, P229
[10]  
FUHLBRIGGE RC, 1987, J IMMUNOL, V138, P3799