Responses of Neutrophils to anti-integrin antibodies depends on costimulation through low affinity FcγRs:: Full activation requires both integrin and nonintegrin signals

被引:35
作者
Jakus, Z
Berton, G
Ligeti, E
Lowell, CA
Mócsai, A
机构
[1] Semmelweis Univ, Sch Med, Dept Physiol, H-1444 Budapest, Hungary
[2] Univ Verona, Dept Pathol, Sect Gen Pathol, I-37100 Verona, Italy
[3] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA
关键词
D O I
10.4049/jimmunol.173.3.2068
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The relative contribution of integrin and nonintegrin signals to neutrophil activation is incompletely understood. Immobilized anti-integrin Abs were previously shown to induce robust activation of neutrophils without any additional stimulus, suggesting that cross-linking of integrins is sufficient for full activation of the cells. However, the possible contribution from other receptors has not been tested in this system. In this study, we show that neutrophil responses to anti-integrin Abs requires costimulation through low-affinity FcgammaRs. Murine neutrophils lacking the FcR gamma-chain or FcgammaRIII failed to respond to immobilized Abs against beta(1), beta(2) or beta(3) integrins and the activation of wild-type cells could be prevented by blocking Abs against FcgammaRII/III. Plate-bound anti-CD18 Abs initiated a respiratory burst from human neutrophils, but this response was abrogated when the F(ab')2 of the same Abs were used or the cells were preincubated with FcgammaRIIA-blocking Abs. Lack of FcgammaRIII or administration of FcgammaR-blocking Abs had no effect on responses of TNF-stimulated cells plated on fibrinogen or rICAM-1. TNF restored the respiratory burst of FcgammaRIII-deficient neutrophils plated on anti-CD18 mAbs. The p38 MAPK inhibitor SB203580 attenuated the responses of neutrophils to anti-CD18 mAbs or TNF stimulation on a fibrinogen surface. Taken together, these results indicate that activation of low-affinity FcgammaRs is required for neutrophil responses induced by anti-integrin Abs and suggest that a second coactivation signal (e.g., through TNF or FcR ligation) is indispensable for full integrin-mediated activation of neutrophils. These second signals are interchangeable and they may converge on the p38 MAPK.
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页码:2068 / 2077
页数:10
相关论文
共 48 条
[1]   GENERATION OF SIGNALS ACTIVATING NEUTROPHIL FUNCTIONS BY LEUKOCYTE INTEGRINS - LFA-1 AND GP150/95, BUT NOT CR3, ARE ABLE TO STIMULATE THE RESPIRATORY BURST OF HUMAN NEUTROPHILS [J].
BERTON, G ;
LAUDANNA, C ;
SORIO, C ;
ROSSI, F .
JOURNAL OF CELL BIOLOGY, 1992, 116 (04) :1007-1017
[2]   BETA-2 INTEGRIN-DEPENDENT PROTEIN-TYROSINE PHOSPHORYLATION AND ACTIVATION OF THE FGR PROTEIN-TYROSINE KINASE IN HUMAN NEUTROPHILS [J].
BERTON, G ;
FUMAGALLI, L ;
LAUDANNA, C ;
SORIO, C .
JOURNAL OF CELL BIOLOGY, 1994, 126 (04) :1111-1121
[3]   Leukocyte adhesion deficiency syndromes:: adhesion and tethering defects involving β2 integrins and selectin ligands [J].
Bunting, M ;
Harris, ES ;
McIntyre, TM ;
Prescott, SM ;
Zimmerman, GA .
CURRENT OPINION IN HEMATOLOGY, 2002, 9 (01) :30-35
[4]   Role for plastin in host defense distinguishes integrin signaling from cell adhesion and spreading [J].
Chen, H ;
Mocsai, A ;
Zhang, H ;
Ding, RX ;
Morisaki, JH ;
White, M ;
Rothfork, JM ;
Heiser, P ;
Colucci-Guyon, E ;
Lowell, CA ;
Gresham, HD ;
Allen, PM ;
Brown, EJ .
IMMUNITY, 2003, 19 (01) :95-104
[5]   Convergence of Fcγ receptor IIA and Fcγ receptor IIIB signaling pathways in human neutrophils [J].
Chuang, FYS ;
Sassaroli, M ;
Unkeless, JC .
JOURNAL OF IMMUNOLOGY, 2000, 164 (01) :350-360
[6]  
Costello PS, 1996, ONCOGENE, V13, P2595
[7]   A critical role for Syk in signal transduction and phagocytosis mediated by Fc gamma receptors on macrophages [J].
Crowley, MT ;
Costello, PS ;
FitzerAttas, CJ ;
Turner, M ;
Meng, FY ;
Lowell, C ;
Tybulewicz, VLJ ;
DeFranco, AL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (07) :1027-1039
[8]  
DACRON M, 1997, ANNU REV IMMUNOL, V15, P203
[9]   LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 (LFA-1) - A SURFACE-ANTIGEN DISTINCT FROM LYT-2,3 THAT PARTICIPATES IN LYMPHOCYTE-T-MEDIATED KILLING [J].
DAVIGNON, D ;
MARTZ, E ;
REYNOLDS, T ;
KURZINGER, K ;
SPRINGER, TA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (07) :4535-4539
[10]   Role of p190RhoGAP in β2 integrin regulation of RhoA in human neutrophils [J].
Dib, K ;
Melander, F ;
Andersson, T .
JOURNAL OF IMMUNOLOGY, 2001, 166 (10) :6311-6322