Functional characterization of receptor-type protein tyrosine phosphatase CD148 (HPTPη/DEP-1) in Fcγ receptor IIa signal transduction of human neutrophils

Activation of the 40-kDa low-affinity receptor for IgG (Fc gamma RIIa, CD32) leads to tyrosine phosphorylation, increase of cytosolic free calcium concentration ([Ca2+](i)), and production of superoxide anions (O-2(-)) 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 gamma RIIa 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 O-2(-) production determined by lucigenin-dependent chemiluminescence were inhibited by co-cross-linking of CD45 with Fc gamma RIIa in comparison to isotype control monoclonal antibody (mAb). In contrast, preincubation with CD148 mAb 143-41 abolished O-2(-) generation, but did not inhibit [Ca2+](i) rise. In summary, both clustered human RPTP, CD45 and CD148, inhibit Fc gamma RIIa-induced O-2(-) production in PMN, but they differ in regulation of [Ca2+](i). Therefore, it is suggested that co-cross-linking of Fc gamma RII with CD45 and CD148 leads to dephosphorylation of different substrates. These distinct functional capacities may be important for differential regulation of Fc gamma R signaling by currently unknown ligands.