Tumor necrosis factor-α-stimulate polymorphonuclear leukocytes suppress migration and bactericidal activity of polymorphonuclear leukocytes in a paracrine manner

被引:14
作者
Grutkoski, PS [1 ]
D'Amico, R
Ayala, A
Simms, HH
机构
[1] Rhode Isl Hosp, Div Surg Res, Providence, RI 02902 USA
[2] Brown Univ, Sch Med, Providence, RI 02912 USA
[3] NYU, Sch Med, N Shore Long Isl Jewish Med Ctr, Manhasset, NY USA
关键词
neutrophil; cross-talk; phagocytosis; migration; oxidative; metabolism; tumor necrosis factor-alpha; cytokine; inflammation; chemokine;
D O I
10.1097/00003246-200203000-00017
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objective: Polymorphonuclear leukocytes (PMN) and tumor necrosis factor-alpha (TNF-alpha) play prominent roles in acute respiratory distress syndrome, ischemia-reperfusion injury, trauma, and sepsis. Whereas direct effects of TNF-a on PMN function and viability are well documented, little data are available addressing the ability of PMN to communicate with each other in response to cytokine stimulation. Therefore, the aim of this study was to determine whether TNF-a. can modulate PMN function by inducing PMN to secrete products upon stimulation, which would affect other PMN in vitro in a manner independent of cell contact. Methods: PMN were purified daily from blood obtained from a pool of 22 healthy volunteers. Conditioned media (CM-TNF) was prepared by incubating PMN in Hanks' balanced salt solution plus TNF-alpha for 1-4 hrs. Freshly isolated PMN were resuspended in CM-TNF and analyzed for 1) phagocytosis of opsonized Escherichia coli, 2) oxidative metabolism as measured as an index of DCF-DA activation, and 3) migration to chemoattractants through Transwell inserts. Results. CM-TNF decreased PMN phagocytotic activity by 8% to 15% and completely suppressed oxidative metabolism but did not modulate the expression of receptors associated with these functions. CM-TNF suppressed the migration of PMN to two biologically relevant agents, N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4, by approximately 65%, but had no effect on PMN migration to interleukin-8. This suppression was observed for migration across plastic filters as well as extracellular matrix proteins. Conclusion: Our data demonstrate that PMN stimulated with TNF-alpha suppress the immunologic function and migration of other PMN independent of cell-cell contact and suggest that TNF-alpha may participate in a negative feedback loop by inducing a PMN-derived factor that counteracts its activity.
引用
收藏
页码:591 / 597
页数:7
相关论文
共 40 条
[1]   Activated polymorphonuclear leukocytes affect red blood cell aggregability [J].
Baskurt, OK ;
Meiselman, HJ .
JOURNAL OF LEUKOCYTE BIOLOGY, 1998, 63 (01) :89-93
[2]  
BERGER M, 1988, BLOOD, V71, P151
[3]   ISOLATION OF LYMPHOCYTES, GRANULOCYTES AND MACROPHAGES [J].
BOYUM, A .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1976, :9-15
[4]   Cytokine-induced sequential migration of neutrophils through endothelium and epithelium [J].
Casale, TB ;
Carolan, EJ .
INFLAMMATION RESEARCH, 1999, 48 (01) :22-27
[5]   Neutrophil-derived proteins: Selling cytokines by the pound [J].
Cassatella, MA .
ADVANCES IN IMMUNOLOGY, VOL 73, 1999, 73 :369-509
[6]   Diverging signal transduction pathways activated by interleukin 8 (IL-8) and related chemokines in human neutrophils - IL-8 and Gro-alpha differentially stimulate calcium influx through IL-8 receptors A and B [J].
Damaj, BB ;
McColl, SR ;
Neote, K ;
Hebert, CA ;
Naccache, PH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (34) :20540-20544
[7]   Adhesion molecules - Their role in health and disease [J].
Etzioni, A .
PEDIATRIC RESEARCH, 1996, 39 (02) :191-198
[8]   Fibronectin enhances the migration rate of human neutrophils in vitro [J].
Everitt, EA ;
Malik, AB ;
Hendey, B .
JOURNAL OF LEUKOCYTE BIOLOGY, 1996, 60 (02) :199-206
[9]  
Feghali CA, 1997, FRONT BIOSCI, V2, P12
[10]  
FERRANTE A, 1993, J IMMUNOL, V151, P4821