Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fcgamma receptor (FcgammaR) engagement is pivotal for many effector functions of macrophages, polymorphonuclear neutrophils (PMN), and natural killer (NK) cells. Mice transgenic for the A and B isoforms of human (h) FcgammaRIII on macrophages, PMN, and NK cells were constructed to permit the study of mechanisms and potential in vivo strategies to utilize the cytotoxic effector and antigen-presenting functions of cells expressing the hFcgammaR. The present report characterizes the phenotypic and functional expression of hFcgammaRIII in transgenic mice derived by crossing hFcgammaRIIIA and hFcgammaRIIIB transgenic mice. Interleukin-2 (IL-2) induces hFcgammaRIII expression by myeloid cells and their precursors, and these transgenic receptors promote in vitro cytotoxicity and anti-hFcgammaRIII antibody internalization. Splenocytes from untreated and IL-2-treated hFcgammaRIIIA, hFcgammaRIIIB, and hFcgammaRIIIA/B mice exhibited enhanced in vitro cytotoxicity toward HER-2/neu-overexpressing SK-OV-3 human ovarian carcinoma cells when incubated with the murine bispecific mAb 2B1, which has specificity for HER-2/neu and hFcgammaRIII. These results indicate that hFcgammaRIII transgenes are expressed on relevant murine cellular subsets, exhibit inducible up-regulation patterns similar to those seen in humans, and code for functional proteins. hFcgammaRIII transgenic mice exhibiting specific cellular subset expression will permit the examination of strategies designed to enhance hFcgammaRIII-dependent immunological effector functions and will provide a model system in which to evaluate preclinically potential candidate molecules that recognize hFcgammaRIII for the immunotherapy of cancer.
 ...
PMID:Production and characterization of mice transgenic for the A and B isoforms of human FcgammaRIII. 1055 May 49

Freshly isolated human polymorphonuclear cells (PMNCs) constitutively express Fcgamma receptor (Fc-gammaR) II and FcgammaRIII on the cell surface but not FcgammaRI. Cytokines such as interferon-gamma (IFNgamma), granulocyte-macrophage colony-stimulating factor (CSF), and granulocyte-CSF trigger FcgammaRI expression on (PMNCs). Because PMNCs express interleukin (IL)-2 receptor, we investigated whether IL-2 can induce FcgammaRI expression on PMNCs isolated from IL-2-treated metastatic renal cell carcinoma (MRCC) and low-grade non-Hodgkin lymphoma (LGNHL) patients. Pretherapy flow cytometry analysis of Fcgamma receptors on PMNCs did not show FcgammaRI expression. Interestingly, 3 days after therapy, PMNCs displayed a detectable amount of FcgammaRI on the cell surface. Kinetic studies on the in vivo effects of IL-2 on MRCC patients showed that FcgammaRI was transiently expressed, starting within 3-6 days of therapy, remaining expressed for 10-15 days, and rapidly declining, whereas such expression remained stable for months in LGNHL patients. In contrast, Fc-gammaRII was not affected. In addition, FcgammaRI+ PMNCs coated in vitro with a bispecific antibody Fab anti-FcgammaRI x anti-HER-2/neu formed intercellular conjugates with a human HER-2/neu-transfected 3T3 cell line (HER-2/neu-3T3). Interleukin-2 treatment increased the number of FcgammaRIII low eosinophils, leading to a change in FcgammaRIII distribution among granulocyte cell subsets. In vitro IL-2 treatment of purified PMNCs failed to generate Fc-gammaRI expression, suggesting that IL-2 indirectly causes FcgammaRI expression. During the IL-2 administration, we did not observe significant changes in IFNgamma serum level. In conclusion, our observation may be used to potentiate the antitumor effects of IL-2 in novel immunotherapy regimens, perhaps by redirecting FcgammaRI+ PMNCs against cancer cells by heteroconjugate antibodies and monitoring the biologic activity of subcutaneous IL-2 in cancer patients.
 ...
PMID:Subcutaneous administration of interleukin-2 triggers Fcgamma receptor I expression on human peripheral blood neutrophils in solid and hematologic malignancies. 1156 39