Down-regulation of CXCR1 and CXCR2 expression on human neutrophils upon activation of whole blood by S-aureus is mediated by TNF-α

被引:38
作者
Tikhonov, I
Doroshenko, T
Chaly, Y
Smolnikova, V
Pauza, CD
Voitenok, N
机构
[1] Ctr Med Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA
[2] Inst Hematol & Blood Transfus, Cellular & Mol Immunol Lab, Minsk, BELARUS
[3] Fund Mol Hematol & Immunol, Moscow, Russia
关键词
interleukin-8; receptors; neutrophils; TNF-alpha; LPS; staphylococcus;
D O I
10.1046/j.1365-2249.2001.01626.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
It was suggested that bacterial products can inhibit the expression of leucocyte chemokine receptors during sepsis and affect leucocyte functions in septic syndrome. Superantigens and toxins produced by Staphylococcus aureus are capable of activating leucocytes via binding to MHC-II antigens on monocytes and T-cell receptor molecules on T lymphocytes. It was recently shown that staphylococcal enterotoxins directly down-regulate the expression of CC chemokine receptors on monocytes through binding to MHC class II molecules. We studied the effects of killed S. aureus on the expression of interleukin-8 receptors, CXCR1 and CXCR2, on polymorphonuclear leucocytes (PMN), which are known to lack the expression of MHC-II antigens. It was shown that S. aureus down-regulated the cell-surface expression of CXCR1 and CXCR2 on PMN in the whole blood and total blood leucocyte fraction containing PMN and monocytes, but did not modulate IL-8 receptor expression in purified PMN suspension. Antibody to TNF-alpha abrogated down-regulation of IL-8 receptors induced by S. aureus. In contrast, LPS reduced CXCR1 and CXCR2 expression in purified PMN and whole blood in a TNF-alpha -independent manner. We further showed that TNF-alpha -induced decrease of CXCR1 and CXCR2 expression was associated with lower IL-8 binding and lower CXCR1 and CXCR2 mRNA levels, and was abrogated by protease inhibitors. We suggest that during septicemia, S. aureus may inhibit neutrophil responsiveness to IL-8 and other CXC chemokines via TNF-alpha- mediated down-regulation of CXCR1 and CXCR2.
引用
收藏
页码:414 / 422
页数:9
相关论文
共 42 条
[1]  
AHUJA SK, 1994, J BIOL CHEM, V269, P26381
[2]  
Asagoe K, 1998, J IMMUNOL, V160, P4518
[3]   Chemokines and leukocyte traffic [J].
Baggiolini, M .
NATURE, 1998, 392 (6676) :565-568
[4]   Superantigens in human disease [J].
Bernal, A ;
Proft, T ;
Fraser, JD ;
Posnett, DN .
JOURNAL OF CLINICAL IMMUNOLOGY, 1999, 19 (03) :149-157
[5]  
BESEMER J, 1989, J BIOL CHEM, V264, P17409
[6]  
Bhattacharya C, 1997, J IMMUNOL, V158, P1293
[7]   Expression of IL-8 gene in human monocytes and lymphocytes: Differential regulation by TNF and IL-1 [J].
Chaly, YV ;
Selvan, RS ;
Fegeding, KV ;
Kolesnikova, TS ;
Voitenok, NN .
CYTOKINE, 2000, 12 (06) :636-643
[8]  
CHUNTHARAPAI A, 1994, J IMMUNOL, V153, P5682
[9]  
CHUNTHARAPAI A, 1994, J IMMUNOL, V152, P1783
[10]  
Cummings CJ, 1999, J IMMUNOL, V162, P2341