Hundt M, Schmidt R E
Medizinische Hochschule Hannover, Abteilung Klinische Immunologie, Germany.
Eur J Immunol. 1997 Dec;27(12):3532-5. doi: 10.1002/eji.1830271255.
Activation of the 40-kDa low-affinity receptor for IgG (Fc gammaRIIa, CD32) leads to tyrosine phosphorylation, increase of cytosolic free calcium concentration ([Ca2+]i), and production of superoxide anions (O2-) in neutrophils (PMN). It has been established that protein tyrosine kinases (PTK) and phosphatases (PTP) are essential for the regulation of intracellular signaling. CD45 is a type I receptor-type protein tyrosine phosphatase (RPTP) with two PTP domains. Recently it has been demonstrated that co-cross-linking of CD45 modulates the signal transduction pathway of Fc gammaRIIa in PMN. In contrast, the functional characteristics of CD148 (HPTP eta/DEP-1), a new RPTP with only one PTP domain, is unknown. CD148 is expressed on PMN in slightly lower density than CD45, and in higher density than on lymphocytes. [Ca2+]i measured with fluo-3-loaded PMN by flow cytometry and O2- production determined by lucigenin-dependent chemiluminescence were inhibited by co-cross-linking of CD45 with Fc gammaRIIa in comparison to isotype control monoclonal antibody (mAb). In contrast, pre-incubation with CD148 mAb 143-41 abolished O2- generation, but did not inhibit [Ca2+]i rise. In summary, both clustered human RPTP, CD45 and CD148, inhibit Fc gammaRIIa-induced O2- production in PMN, but they differ in regulation of [Ca2+]i. Therefore, it is suggested that co-cross-linking of Fc gammaRII with CD45 and CD148 leads to dephosphorylation of different substrates. These distinct functional capacities may be important for differential regulation of Fc gammaR signaling by currently unknown ligands.
免疫球蛋白G（IgG）的40 kDa低亲和力受体（FcγRIIa，CD32）的激活会导致酪氨酸磷酸化、中性粒细胞（PMN）胞质游离钙浓度（[Ca2+]i）升高以及超氧阴离子（O2-）的产生。已经确定蛋白酪氨酸激酶（PTK）和磷酸酶（PTP）对于细胞内信号传导的调节至关重要。CD45是一种具有两个PTP结构域的I型受体型蛋白酪氨酸磷酸酶（RPTP）。最近已经证明，CD45的共交联可调节PMN中FcγRIIa的信号转导途径。相比之下，一种仅具有一个PTP结构域的新型RPTP，即CD148（HPTP eta/DEP-1）的功能特性尚不清楚。CD148在PMN上的表达密度略低于CD45，高于淋巴细胞。与同型对照单克隆抗体（mAb）相比，通过流式细胞术用fluo-3标记的PMN测量的[Ca2+]i以及通过鲁米诺依赖性化学发光测定的O2-产生，在CD45与FcγRIIa共交联时受到抑制。相反，用CD148 mAb 143-41预孵育可消除O2-的产生，但不抑制[Ca2+]i升高。总之，聚集的人RPTP，CD45和CD148，均抑制PMN中FcγRIIa诱导的O2-产生，但它们在[Ca2+]i的调节上有所不同。因此，有人提出FcγRII与CD45和CD148的共交联会导致不同底物的去磷酸化。这些不同的功能能力对于目前未知配体对FcγR信号的差异调节可能很重要。
