C-Reactive Protein Triggers Calcium Signalling in Human Neutrophilic Granulocytes via FcRIIa in an Allele-Specific Way

被引:7
作者
Aas, V. [1 ]
Sand, K. L. [2 ]
Asheim, H-C [1 ]
Benestad, H. B. [2 ]
Iversen, J-G [2 ]
机构
[1] Oslo & Akershus Univ Coll Appl Sci, Fac Hlth Sci, N-0130 Oslo, Norway
[2] Univ Oslo, Dept Physiol, Inst Basic Med Sci, Oslo, Norway
关键词
FC-GAMMA-RIIA; SPHINGOSINE KINASE; INTERFERON-GAMMA; HUMAN MONOCYTES; RECEPTOR; EXPRESSION; DISEASE; INFLAMMATION; MOBILIZATION; POLYMORPHISM;
D O I
10.1111/sji.12049
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
C-reactive protein (CRP) binds to Fc-receptors, FcRIIa (CD32) with high affinity and to FcRIa (CD64) with low affinity. The binding to CD32 has been shown to be allele specific, that is, it binds to R/R131 but not to H/H131. Little is known about the cooperation of CRP and neutrophilic granulocytes (PMNs) in inflammatory reactions. The purpose of the present study was to examine CRP signalling in human PMNs, and whether this signalling is also allele specific. Cytosolic calcium of PMN was measured in a single-cell digital imaging system. Receptor expression and polymorphism were studied by real-time RT-PCR, flow cytometry and standard PCR. C-reactive protein induced cytosolic calcium signals in PMNs from homozygote R/R131donors, but not in PMNs from heterozygote R/H131 donors. However, after the heterozygote PMNs had been incubated with IFN- (100U/ml) for 2h, both the proportion of cells responding and the size of the CRP-induced calcium signals increased. IFN- increased mRNA expression of CD64 about fivefold and surface protein expression of CD64 about fourfold. The calcium signal elicited by CRP was augmented by PMN adhesion to fibronectin, but almost totally abrogated by sphingosine kinase inhibitors. The signals were partly dependent on calcium influx. In conclusion, calcium signalling instigated by CRP in human PMN is FcRIIa allele specific, as R/R131 responded to CRP, whereas R/H131 did not. However, increased expression of FcRIa (CD64), stimulated by IFN-, can augment calcium signalling by CRP in low-responders. This suggests that the state of the PMNs, as well as the genetic origin, affect sensitivity for CRP.
引用
收藏
页码:442 / 451
页数:10
相关论文
共 49 条
[31]   ON THE INTERACTION OF IGG SUBCLASSES WITH THE LOW AFFINITY FC-GAMMA-RIIA (CD32) ON HUMAN MONOCYTES, NEUTROPHILS, AND PLATELETS - ANALYSIS OF A FUNCTIONAL POLYMORPHISM TO HUMAN IGG2 [J].
PARREN, PWHI ;
WARMERDAM, PAM ;
BOEIJE, LCM ;
ARTS, J ;
WESTERDAAL, NAC ;
VLUG, A ;
CAPEL, PJA ;
AARDEN, LA ;
VANDEWINKEL, JGJ .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (04) :1537-1546
[32]   Regulation of sphingosine kinase and sphingolipid signaling [J].
Pitson, Stuart M. .
TRENDS IN BIOCHEMICAL SCIENCES, 2011, 36 (02) :97-107
[33]   C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus [J].
Pradhan, AD ;
Manson, JE ;
Rifai, N ;
Buring, JE ;
Ridker, PM .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 286 (03) :327-334
[34]   C-reactive protein increases oxygen radical generation by neutrophils [J].
Prasad, K .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, 2004, 9 (03) :203-209
[35]   Donor dependent, interferon-γ induced HLA-DR expression on human neutrophils in vivo [J].
Reinisch, W ;
Lichtenberger, C ;
Steger, G ;
Tillinger, W ;
Scheiner, O ;
Gangl, A ;
Maurer, D ;
Willheim, M .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2003, 133 (03) :476-484
[36]  
RICHARDSON MD, 1991, MYCOSES, V34, P141, DOI 10.1111/j.1439-0507.1991.tb00635.x
[37]   C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women [J].
Ridker, PM ;
Hennekens, CH ;
Buring, JE ;
Rifai, N .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (12) :836-843
[38]   Neutrophil responses to CRP are not dependent on polymorphism of human FcγRIIA (R131H) [J].
Rodríguez, JA ;
Bodman-Smith, KB ;
Raynes, JG .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2004, 138 (02) :271-277
[39]  
ROSALES C, 1992, J BIOL CHEM, V267, P5265
[40]   QUANTITATIVE-ANALYSIS OF CYTOSOLIC-FREE CALCIUM OSCILLATIONS IN NEUTROPHILS BY MATHEMATICAL-MODELING [J].
ROTNES, JS ;
ROTTINGEN, JA .
CELL CALCIUM, 1994, 15 (06) :467-482