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Biomedical subjects

P Ralph

Publications and source records attributed to P Ralph.

At least 109 records · Page 6Linked to original sources
PubMed1980

All classes of murine IgG antibody mediate macrophage phagocytosis and lysis of erythrocytes.

Antibody-dependent phagocytosis and lysis of sheep RBC by mouse peritoneal exudate cells were studied using IgG subclass fractions of sera prepared by protein A-Sepharose chromatography. Three IgG1, 3 IgG2a, 4 IgG2b, and 1 IgG3 hybridoma antibodies to RBC were also used. The results showed that some monoclonal IgG2a and IgG2b antibodies were more active than IgG1 or IgG3 preparations when normalized to hemagglutinating activity, but all IgG sources mediated both effector mechanisms. This is in accord with findings of strong Fc receptors on macrophages for the IgG2 isotypes and weaker binding by IgG1 and newly discovered IgG3 receptors. A monoclonal IgG2b with no hemagglutination titer showed normal cooperation with macrophages. In contrast, 2 hybridoma IgM were inactive in macrophage-mediated lysis and allowed only marginal ingestion. Similar results were obtained using several macrophage cell lines, mouse spleen and human peripheral blood mononuclear cells, showing that all these types of effector cells do not distinguish among (mouse) IgG subclasses in handling antibody-coated RBC.

Animals↗
PubMed1979

Induction of prostaglandin E synthesis in normal and neoplastic macrophages: role for colony-stimulating factor(s) distinct from effects on myeloid progenitor cell proliferation.

The biosynthesis of prostaglandin E (PGE) by normal and neoplastic macrophages is intrinsically linked to their synthesis of, and exposure to, myeloid colony-stimulating factors (CS-factors). The defect in responsiveness to endotoxin lipopolysaccharide (LPS) by macrophages from C3H/HeJ mice extends equally to the synthesis of CS-factor and PGE. However, C3H/HeJ macrophages can be stimulated to synthesize PGE by treatment with agents other than LPS [zymosan, tuberculin purified protein derivative, concanavalin A, poly(I).poly(C)], which also stimulate CS-factor production, or by the addition of various preparations of soluble CS-factor. In peritoneal wash preparations, constitutive PGE synthesis occurred in rapidly sedimenting macrophage cells, whereas constitutive CS-factor production and inducible PGE synthesis occurred in slower sedimenting adherent cells. A similar functional heterogeneity in CS-factor and PGE production was found in neoplastic macrophagae cell lines. The association of elevated CS-factor levels and PGE synthesis by macrophages suggests a role for CS-factor in many of the physiological responses heretofore associated with elevated tissue levels of the E type prostaglandins.

Animals↗
PubMed1979

Macrophage factor controlling differentiation of B cells.

Peritoneal macrophages of the mouse produce, in response to cell wall components of Gram-negative bacteria (lipopolysaccharide and lipoproteins), a factor that causes antigen-stimulated B cells of differentiate into antibody-producing cells. Unlike lipopolysaccharide, this factor is not mitogenic for B cells. Production of the macrophage factor does not depend on participation of T cells or other accessory cells since it is readily produced by several cloned macrophage cell lines as well as by peritoneal macrophages of athymic nude mice. The factor is active only in conjunction with antigen. T cells, although apparently not necessary, amplify its effect. The factor induces phenotypic differentiation of B cell precursors as selectively as thymopoietin induces differentiation of prothymocytes.

Animals↗
PubMed1979

Matching of chemotherapy to mouse strain and lymphoid tumor type to prevent tumor-induced suppression of specific T- and B-cell functions.

Specific immunological and hematopoietic functions were studied during treatment with antineoplastic agents in mice bearing syngeneic lymphoid tumors: 70Z/2, a B-cell lymphoma of C57BL X DBA/2 F1 (hereafter called (BD2F1) mice; EL4, a T-cell lymphoma of C57BL/6 mice; or J774, a macrophage tumor of BALB/c mice. Both B- and T-lymphocyte function (antibody-forming cells and cell-mediated lymphocyte lympholysis toward alloantigens) were suppressed in spleen cells of mice bearing these tumors. Other hematopoietic functions (granulocyte, macrophage, and megakaryocyte progenitor cells) were variably influenced by growth of these lymphoid tumors. J774 enhanced, but 70Z/2 suppressed, megakaryocyte progenitor cells. J774 and 70Z/2 increased levels of granulocyte-macrophage progenitor cells. EL4, the T-cell lymphoma, did not influence either cell type. Significant variation in strain sensitivity to drug toxicity and drug effectiveness in different tumor-host systems was observed. Increased median survival time with reversal of tumor-induced immune dysfunction, without toxicity to hematopoietic progenitor cells, was realized in two tumor-host-drug combinations. Polyinosinic-polycytidylic acid was effective against J774, while actinomycin D was active against 70Z/2. Mitomycin C effectively reduced tumor load, as evidenced by loss of splenic tumor colony-forming cells for all three tumors. This agent prolonged survival and concomitantly restored immunological responsiveness in hosts immunosuppressed by growth of 70Z/2 or J774. Paralleling tumor reduction with mitomycin C therapy, the splenic hematopoietic progenitor and colony-forming B-cells were reduced in tumor-bearing and tumor-free mice, thus compromising its therapeutic effectiveness. 1-beta-D-Arabinofuranosylcytosine reduced tumor load with marginal toxicity toward hematopoietic progenitor and colony-forming B-cells. However, immune responsiveness was only partially restored, and median survival was not increased. The results presented show the diversity of therapeutic drug effectiveness in increasing mean survival time and influencing other life-sustaining parameters (immunological and hematopoietic functions).

Animals↗
PubMed1979

Sensitivity to chemotherapeutic and immunomodulating agents of two mouse lymphomas and of a macrophage tumor.

The effect of treatment with 15 chemotherapeutic and 10 immunomodulating agents on the growth of T-cell lymphoma EL-4, macrophage tumor J774, and B-cell lymphoma 70Z/2 of the mouse has been studied using the prolongation of median survival time of tumor-bearing hosts as an index of therapeutic effectiveness. The survival time of mice bearing 70Z/2 was prolonged more than 100% by single-agent therapy with actinomycin D, cyclophosphamide, 6-mercaptopurine, mitomycin C, and vinblastine; a similar response of J774 was produced by therapy with Adriamycin, cyclophosphamide, or 6-mercaptopurine. No chemotherapeutic agent prolonged the median survival time of mice bearing EL-4 by 100% or more. Of the immunomodulating agents, mycobacterial preparations (Bacillus Calmette-Guérin or interphase material), Corynebacterium parvum, and polyinosinic-polycytidylic acid moderately prolonged the survival time of mice bearing J774 or 70Z/2; the EL-4 lymphoma was refractory to all 10 immunomodulating agents.

Adrenal Cortex Hormones↗
PubMed1978

Immunologic functions and in vitro activation of cultured macrophage tumor lines.

Five murine monocyte of macrophage tumor lines adapted to culture were characterized for differentiated properties. They ingested zymosan and latex beads, bore receptors for immunoglobulin and complement, synthesized lysozyme (most of which was secreted), and produced granulocyte colony-stimulating activity, either spontaneously or inducibly. Some of the lines also mediated phagocytosis and exocytosis of red blood cells (RBC) and lysis of tumor targets, dependent on the presence of specific antitarget sera. All the lines were growth inhibited by zymosan and Mycobacterium bovis BCG, but not by latex beads. Other macrophage-activating agents, dextran sulfate and lipopolysaccharide (LPS), as well as tuberculin purified protein derivative (PPD), inhibited most of the lines. Except for Fc and C receptors, most of the above properties were not found with other types of hematopoietic tumors in culture. In attempts to activate the macrophage lines in vitro to the "angry" state, we found that preincubation with concentrations of LPS and PPD cytostatic to the cells stimulated antibody-dependent RBC lysis, but not antibody-independent or tumor cytolysis. A classification of monocyte-related tumors and normal cells is proposed based on functional activities and differential sensitivity to immunostimulating agents.

Animals↗
PubMed1978

Induction of myeloid colony-stimulating activity in murine monocyte tumor cell lines by macrophage activators and in a T-cell line by concanavalin A.

Certain fibrosarcoma lines in culture and the WEHI-3 myelomonocytic leukemia cell line have previously been shown to secrete myeloid colony-stimulating activity (CSA) spontaneously. We describe here other hematopoietic tumor cell lines in which CSA is either produced constitutively or inducible by immunostimulators. CSA production in macrophage and monocyte tumor lines is induced by lipopolysaccharide, zymosan, Mycobacterium strain Bacillus Calmette-Guérin, tuberculin purified protein-derivative preparation from mycobacteria, and dextran sulfate. Myeloma, mastocytoma, and T-lymphoma lines do not produce CSA with or without these agents. In contrast, the T-lymphocyte mitogen concanavalin A (but not phytohemagglutinin) induces CSA synthesis in one of seven T-lymphomas tested. In most cases induction of CSA is correlated with conditions of cell growth inhibition by the immunomodulators. However, other drugs that cause cytostasis or cytotoxicity do not lead to CSA production. Leukemic cells thus may retain sensitivity to normal regulatory events with resultant effects on host hematopoietic cell functions.

Animals↗
PubMed1978

Corticosteroids block newly induced but not constitutive functions of macrophage cell lines: myeloid colony-stimulating activity production, latex phagocytosis, and antibody-dependent lysis of RBC and tumor targets.

Hydrocortisone at 10(-4) M added to macrophage cell lines had no effect on the following activities: J774.1 antibody-dependent phagocytosis and lysis of sheep RBC, RAW 264 antibody-dependent lysis of tumor targets, latex bead phagocytosis by PU5-1.8 cells, and constitutive production of myeloid colony-stimulating activity (CSA) by WEHI-3 cells. In contrast, 10(-4) M hydrocortisone completely inhibited LPS or PPD activation of the following functions: induced production of myeloid CSA, stimulation of latex phagocytosis and stimulation of antibody-dependent lysis of tumor targets by PU5-1.8 cell line, and stimulation of antibody-dependent lysis of RBC targets by RAW 264 cell line. Lower concentrations of hydrocortisone or dexamethasone at 10(-6) M inhibited the LPS induction of CSA from 55 to 90%. Growth inhibition of PU5-1.8 cells caused by 1 microgram/ml LPS was also partially reversed by corticosteroids. Thus, steroids block these newly induced but not constitutive functions of these macrophage cells in culture.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

Immunostimulators induce granulocyte/macrophage colony-stimulating activity and block proliferation in a monocyte tumor cell line.

Monocyte tumor cell line PU5-1.8 does not normally produce colony-stimulating activity (CSA) required by granulocyte and macrophage progenitors to proliferate and mature in agar. However, CSA is induced in the culture line by as little as 10 ng/ml endotoxic lipopolysaccharide (LPS), with maximum CSA production and release to the medium between 2 and 3 days of incubation. Derived lipid A, but not alkali-treated LPS, is also active. Induction requires RNA and protein synthesis, but is not blocked by mitomycin C or Colcemid. Other inducers of CSA include Mycobacterium Bacillus Calmette-Guérin, tuberculin protein preparation purified protein derivative, zymosan, and phorbol myristate. All inducing agents are specific inhibitors of the monocyte tumor cell proliferation in vitro. Latex beads, another macrophage-activating agent, are rapidly phagocytosed by PU5-1.8 cells, but neither inhibit growth nor induce CSA.

Animals↗