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C G Figdor

Publications and source records attributed to C G Figdor.

At least 145 records · Page 8Linked to original sources
PubMed1990

IL-4 decreases Fc gamma R membrane expression and Fc gamma R-mediated cytotoxic activity of human monocytes.

Monocytes can express three classes of FcR for IgG: Fc gamma RI, Fc gamma RII, and Fc gamma RIII (CD64, CD32, and CD16, respectively) of which the Fc gamma RIII is expressed after prolonged culture. Fc gamma R expression is regulated by IFN-gamma. Because IFN-gamma and IL-4 have antagonistic effects on the expression of the FcR for IgE on human monocytes, we studied the effect of IL-4 on Fc gamma R expression and function. We show that IL-4 down-regulates Fc gamma RI, Fc gamma RII, and Fc gamma RIII expression of cultured monocytes and inhibits IFN-gamma enhanced Fc gamma RI expression. Exposure of monocytes to IL-4 for 40 h resulted in a dose-dependent decrease of the expression of all three Fc gamma R that persisted throughout the whole culture period (7 days). Anti-IL-4 antibodies completely reversed the IL-4 effect. In addition the impaired Fc gamma R expression correlated directly with reduced Fc gamma R-mediated function because monocytes cultured in the presence of IL-4 have a reduced capacity to lyse human E opsonized with human IgG anti-D or mouse antiglycophorin A antibodies. These observations, together with the previous finding that IL-4 induces Fc epsilon RIIb expression on monocytes, indicate that IL-4 and IFN-gamma may control the Fc gamma R-mediated immune response by differentially regulating Fc gamma R expression.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

IFN-alpha and IFN-gamma have different regulatory effects on IL-4-induced membrane expression of Fc epsilon RIIb and release of soluble Fc epsilon RIIb by human monocytes.

We used highly purified human monocytes to study the regulation of cell surface and secretion of the low affinity FcR for IgE (Fc epsilon RIIb). IL-4 induces Fc epsilon RIIb expression and soluble Fc epsilon RIIb release in a dose-dependent manner. Significant levels of Fc epsilon RIIb expression were obtained after 12 h of incubation with IL-4 and maximal expression was observed between 24 to 48 h after which the expression declined. Surface expression was followed by secretion of soluble Fc epsilon RIIb which reached maximal levels after 3 to 4 days of incubation and which remained constant throughout 7 days of culture. Induction of Fc epsilon RIIb expression by IL-4 was completely blocked by anti-IL-4 antibodies. Furthermore, IL-1 alpha, IL-2, IL-5, granulocyte-macrophage-CSF, IFN-alpha, IFN-gamma, low m.w. BCGF and also LPS all failed to induce Fc epsilon RIIb expression, demonstrating the specificity of the induction. Fc epsilon RIIb membrane expression induced by IL-4 was reduced in the presence of IFN-gamma and IFN-alpha. Strong inhibition of IL-4-induced Fc epsilon RIIb expression was observed at IFN-alpha concentrations of 450 U/ml (80%), and 100 U/ml of IFN-gamma reduced IL-4-induced Fc epsilon RIIb expression by 70%. Interestingly, soluble Fc epsilon RIIb release was strongly inhibited by IFN-alpha. In contrast, IFN-gamma did not affect soluble Fc epsilon RIIb release, suggesting that reduced membrane expression of Fc epsilon RIIb observed in the presence of IFN-gamma does not reflect inhibition of Fc epsilon RIIb expression but may represent enhanced cleavage or reduced anchoring in the membrane of Fc epsilon RIIb. Finally, IL-5 that has been shown to enhance IL-4-induced Fc epsilon RII on B cells does not enhance significantly IL-4-induced Fc epsilon RIIb membrane expression or subsequent soluble Fc epsilon RIIb release by monocytes. Taken together these results show that IFN-alpha and IFN-gamma have different regulatory effects on IL-4-induced Fc epsilon RIIb membrane expression and soluble Fc epsilon RIIb release by human monocytes.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1990

Expression of neural cell adhesion molecule-related sialoglycoprotein in small cell lung cancer and neuroblastoma cell lines H69 and CHP-212.

Monoclonal antibodies (MAbs) 123C3 and 123A8 generated against a membrane preparation of a small cell lung carcinoma (SCLC) specimen recognize not only SCLC and bronchial carcinoids but also a significant portion of non-small cell lung carcinomas (non-SCLC) of various histological types. Together with 13 other monoclonal antibodies, which show preference for SCLC, they have been ranked as SCLC cluster 1 (SC-1) Mabs. In this study we show that SC-1 MAbs are directed against a restricted number of epitopes, and that SC-1 MAbs and a polyclonal antiserum directed against the neural cell adhesion molecule (NCAM) recognize identical glycoproteins, indicating that SC-1 antigens are closely related to or identical with NCAM. Long polysialic acid units composed of alpha-(2,8)-linked N-acetylneuraminic acid units, which in mammals are found exclusively on NCAM, were present on SC-1 antigens in SCLC. This provides further evidence that SC-1 MAbs recognize NCAM. The SC-1 antigens in the SCLC cell line H69 were present in two forms, NCAM-containing alpha-(2,8)-polysialic acid units identified by antiserum 735, the NCAM-H form, and the less sialylated NCAM-L form. The NCAM-H form consisted of diffusely migrating sialoglycoproteins with a molecular weight of 200,000-250,000, which resolved after neuraminidase treatment into two proteins with molecular weights of 140,000 and 180,000. Since the NCAM-H form is expressed in the lung tumor type with a poor prognosis, our results suggest that NCAM might be implicated in the invasive behavior of these NCAM-positive lung tumors.

Antibodies, Monoclonal↗
PubMed1990

Activation and expansion of tumour-infiltrating lymphocytes by anti-CD3 and anti-CD28 monoclonal antibodies.

Cytotoxic T lymphocytes from healthy donors can be expanded to high numbers from the peripheral blood using combinations of anti-CD3 and anti-CD28 monoclonal antibodies (mAb). We investigated whether these antibodies could also be used to induce outgrowth of tumour-infiltrating lymphocytes (TIL) from tumour tissue. In the initiation phase of TIL culture immobilized anti-CD3 antibodies together with anti-CD28 mAb and low-dose interleukin-2 induced a rapid expansion of T cells from various human tumour tissues. The cultured cells showed high levels of cytotoxic T lymphocyte activity, but low levels of lymphokine-activated killer cell activity were generated. This study shows that TIL can be efficiently expanded from tumour tissue by combinations of anti-CD3 and anti-CD28 antibodies. This protocol for cell expansion in vitro may substantially reduce the time required to reach sufficient numbers of TIl for re-infusion to the patient.

Antibodies, Monoclonal↗
PubMed1990

Expression of a human homing receptor (CD44) in lymphoid malignancies and related stages of lymphoid development.

Lymphocyte adhesion to high endothelial venules, a central step during extravasation into lymphoid tissues, involves an 85 to 95-kD class of lymphocyte surface glycoproteins, which fall in the cluster of CD44 antigens. In this paper we describe the expression of this homing receptor glycoprotein during lymphoid development. CD44 expression was examined on a large panel of non-Hodgkin's lymphomas (n = 234) and lymphoid leukemias (n = 44). These tumors, which are the malignant counterparts of normal lymphoid cells "frozen" at a certain stage of maturation/activation, are thought to represent a complete spectrum of lymphoid development from stem cell to mature, activated T and B lymphocyte. It was found that CD44 exhibits a trimodal distribution on developing lymphocytes of both the T and B lineage: the CD44 antigen is expressed at relatively high levels during early stages of lymphoid differentiation, i.e., on prothymocytes and immature precursor B cells (null acute lymphoblastic leukemia (ALL) and common ALL). Subsequently, at the stage of the immature/common thymocyte, the pre-B cell and early B cell (pre-B-ALL and B-ALL), the CD44 antigen is temporarily lost from the cell surface to be reacquired during further T and B cell maturation. At the activated (germinal center) B cell stage. CD44 is heterogeneously expressed. This distribution pattern of the CD44 molecule closely matches the recirculatory versus sessile nature of lymphoid cells at consecutive phases of their development, and thus apparently reflects its homing receptor function. In addition, the relatively high expression of the CD44 antigen in the earliest phases of T and B cell development suggests that the molecule may also be involved in the migration of bone marrow derived lymphoid precursors to their site of maturation.

Antigens, Differentiation↗
PubMed1989

Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes.

The lymphocyte function-associated molecule LFA-1 (CD11a/CD18) plays a key part in lymphocyte adhesion. Lymphocytes do not adhere spontaneously; activation of protein kinase C (PKC) by phorbol esters, however, gives rise to strong LFA-1-dependent adhesion, indicating that activation of LFA-1 is required to induce cell adhesion. We have now investigated whether the functionally important CD2 and CD3 surface structures on T lymphocytes are involved in the activation of LFA-1. The stimulation of these molecules, which causes activation of PKC, strongly promoted LFA-1-dependent adhesion. Furthermore, we demonstrate by using cells from an LFA-1-deficient patient that this enhanced lymphocyte adhesion is caused by activation of the LFA-1 molecule and not by activation of its ligands. LFA-1 was persistently activated by triggering through CD2 but only transiently by triggering through CD3. We postulate that CD2 and CD3 can differentially regulate the affinity of LFA-1 for its ligands by modulating its molecular conformation through PKC-dependent mechanisms.

Antigens, CD↗
PubMed1989

Rapid densitometric determination of cell migration and cell adhesion in a microchemotaxis chamber.

A new rapid staining and measuring method has been developed for the quantification of migrated cells in a microchemotaxis chamber. The migrated cells were, after staining, evaluated by a transmission densitometer. The method introduced here is more accurate and faster than those described previously. In addition the technique can be used to determine the adherent capacity of cells.

Cell Adhesion↗
PubMed1989

Ternary representation of trivariate data.

A new fast trivariate display technique based on the ratio of three measured variables and of relative cell number, obtained from flow cytometric measurements, is described.

Data Interpretation, Statistical↗
PubMed1989

Characterization of a novel myeloid antigen regulated during differentiation of monocytic cells.

The monoclonal antibody HC1/6 generated against phorbol 12-myristate 13-acetate-treated U-937 cells recognizes a new cell surface antigen with a broad relative molecular mass ranging from 100 to 150 kDa. This antigen is also present on monocytes, platelets and endothelial cells and is weakly expressed by granulocytes. In contrast, it is absent from T, B and erythroblastoid cells. The antigen HC1/6 is also expressed by normal tissue macrophages in tonsil, lung and kidney, as well as in skin biopsies from pathologies such as sarcoidosis and lepromatous leprosy. The expression of the HC1/6 antigen is increased up to 5-fold when U-937 (promonocytic) and HL-60 (myelomonocytic) cell lines are stimulated with phorbol 12-myristate 13-acetate. Conversely, the expression of the HC1/6 antigen is down-regulated in monocytes upon treatment with interferon-gamma. These findings are discussed in relation with other myeloid cell surface markers.

Antibodies, Monoclonal↗
PubMed1989

Expression of lymphocyte homing receptor as a mechanism of dissemination in non-Hodgkin's lymphoma.

To investigate whether the lymphocyte homing receptor (LHR), an adhesion molecule believed to play an important role in the control of normal lymphocyte circulation, influences the spread of non-Hodgkin's lymphoma (NHL), expression of LHR was examined in 107 NHL of various histologic and immunophenotypic subclasses. This analysis revealed that whereas NHL with a putative derivation from recirculating mature T and B lymphocytes almost invariably express high levels of LHR, those akin to sessile mature or immature lymphocytes tend to express lower levels of LHR. Furthermore, in a survey among diffuse large-cell lymphomas of the B-lineage, the tumors of 11 of 13 patients with stage III/IV disease expressed moderate to high levels of LHR, whereas only two of 17 patients with stage I/II disease had tumors that did so. These findings suggest that LHR is involved in the dissemination of NHL.

Antibodies, Monoclonal↗
PubMed1988

A monoclonal antibody (NKI-L16) directed against a unique epitope on the alpha-chain of human leukocyte function-associated antigen 1 induces homotypic cell-cell interactions.

In the present study a unique antibody (NKI-L16) reacting with the alpha-chain of the human leukocyte function-associated Ag-1 (LFA-1) is described, which stimulates homotypic cell-cell interactions in a manner very similar to 12-O-tetradecanoyl-phorbol-13-acetate (TPA), in contrast to other anti-LFA-1 mAb which inhibit cell aggregation. The induction of aggregate formation of EBV-transformed B cells (JY) and CTL clones by TPA or NKI-L16 is not accompanied by an increase in the expression of LFA-1. Nevertheless, this cluster formation is LFA-1 dependent, inasmuch as anti-LFA-1 antibodies, other than NKI-L16, completely abrogate aggregation. Simultaneous addition of NKI-L16 and TPA did not result in a further increase of the speed of cluster formation, suggesting that a similar pathway is activated. Immunoprecipitation and enzyme digestion studies revealed that NKI-L16 recognizes a unique epitope on the alpha-chain of LFA-1, most likely situated close to the transmembrane segment of the molecule. It is hypothesized that NKI-L16 or TPA can cause the LFA-1 molecule to convert from an inactive to an active configuration, thereby permitting binding of LFA-1 to its natural ligand.

Animals↗
PubMed1988

Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4.

Highly purified peripheral blood monocytes were cultured in the presence of rIL-4. Major changes in the morphology of the monocytes were observed. After day 5 of culturing the cells acquired a macrophage-like appearance, with increased cell size and extensive processes, suggesting that IL-4 may induce monocyte-macrophage differentiation. This notion is supported by the observed increased expression of MHC class II Ag, which is thought to be associated with monocyte differentiation. Exposure of monocytes to IL-4 resulted in a dose-dependent increase of the expression of MHC class II Ag, which became apparent after only 20 h of incubation. Maximal expression was obtained after incubation for 6 days, and persisted throughout the whole culture period. Similarly, IL-4 increased the expression of R for C3bi and p150.95 Ag, two members of the leukocyte function-associated Ag 1 family, whereas the expression of the third member, leukocyte function-associated Ag 1, remained unchanged during culture. Furthermore, it was shown that IL-4 inhibited the secretion of cytostatic and chemotactic compounds. Supernatants of monocytes cultured with IL-4 were, in contrast to control cultures, much less effective in inhibiting the growth of A375 melanoma cells. In addition, these supernatants failed to direct the migration of freshly isolated monocytes in a chemotaxis assay. Further analysis revealed that these supernatants exhibited reduced IL-1 activity, as measured in a mouse thymocyte proliferation assay, which might explain the low cytostatic and chemotactic activity. Taken together these results show that IL-4 modulates monocyte phenotype and function and may induce monocyte-macrophage differentiation in vitro.

Antigens, Surface↗
PubMed1988

Osmotic response of lymphocytes measured by means of forward light scattering: theoretical considerations.

Recent data provide solid experimental evidence that increase in cell size of human lymphocytes, caused by osmotic stress, is not directly proportional to forward scattering intensity but rather is inversely proportional. Here, we provide arguments that this phenomenon can be quantitatively explained by means of a model based on a modified Rayleigh-Debye-Gans theory. As a consequence, the current view that forward scattering intensities can be used as a measure of gross cell size needs to be reconsidered. In addition, we postulate that structural changes of the cytoplasm, imposed by an osmotic stress, reflect corresponding changes in the nucleus.

Flow Cytometry↗
PubMed1987

Membrane glycoprotein p150,95 of human cytotoxic T cell clone is involved in conjugate formation with target cells.

The p150,95 heterodimer, one of three members of the leukocyte function associated antigen (LFA) family, is expressed by monocytes, granulocytes, NK cells, and a small percentage of lymphocytes. We now report that the p150,95 glycoprotein is expressed by some cytotoxic T cell clones and that it is involved in cell-mediated cytolysis by these clones. Two CTL clones, clone JS-93 (CD3+ CD4+ CD8-) and clone JS-102 (CD3+ CD4- CD8+) expressed high levels of p150,95 and were shown to be specifically directed against HLA-DR and HLA-A2, respectively. Immunoprecipitations followed by two-dimensional gel electrophoresis demonstrated no heterogeneity in the p150,95 molecule isolated from both clones. Furthermore, we demonstrated that monoclonal antibodies (moab) directed against p150,95 could inhibit the cytotoxic activity of both clone JS-93 and clone JS-102 (50% and 47%, respectively). Single cell assays revealed the inhibition to occur at the level of conjugate formation rather than at the level of the lethal hit. Similar results were obtained with moab directed against LFA-1 (p170,95). The capacity of the moab directed against LFA-1 and p150,95 to inhibit CTL activity and conjugate formation were additive, resulting in a similar percentage of inhibition as found with moab directed against the common beta-chain of these molecules. It is concluded that at least some CTL clones express the p150,95 antigen at their cell surface, and that this molecule, like LFA-1, acts at the level of conjugate formation between effector and target cells.

Antibodies, Monoclonal↗
PubMed1987

Spectral analysis of flow cytometric data: design of a special-purpose low-pass digital filter.

Spectral decomposition of flow cytometric datafiles of arbitrary dimension reveal information of both the signal and the noise components that constitute the histograms. This spectral information is used to construct a low-pass digital filter, which removes the high-frequency noise from the actual data. It is shown that this procedure guarantees non-trivial smoothing of the flow cytometric data in accordance with the local experimental situation. As a consequence optimal reconstruction of the signal is possible, which facilitates unambiguous interpretation of the data files and mathematical estimation of the statistical parameters.

Flow Cytometry↗