PubMed Health⌕ Search

Biomedical subjects

D O Adams

Publications and source records attributed to D O Adams.

At least 91 records · Page 5Linked to original sources
PubMed1984

Fc-receptor mediated protein phosphorylation in murine peritoneal macrophages.

The effect of Fc receptor engagement on protein phosphorylation in murine peritoneal macrophages has been investigated. Treatment of macrophage cultures with insoluble immune complexes resulted in enhanced phosphorylation of six proteins at 73, 66, 53, 37, 31 and 25 kD. Comparison of the protein phosphorylation patterns induced by immune complexes with those induced by agents which mimic the actions of well known intracellular second messengers (i.e., A23187, dibutyryl cAMP, or phorbol myristate acetate) revealed substantial similarity between Fc receptor induced events and those induced in response to phorbol diesters. There were, however, two phosphorylated proteins which were only seen following stimulation with immune complexes. Thus, more than one kind of protein kinase activity appears to be involved in Fc receptor mediated stimulation of macrophage function.

Animals↗
PubMed1984

Murine monocytes express transferrin receptors: evidence for similarity to inflammatory macrophages.

Nonionic detergent extracts of murine monocytes contain a specific, high-affinity binding site for the serum glycoprotein transferrin. The binding activity was saturable and specific for 125I-labeled transferrin. The transferrin-receptor content of monocytes was compared with that of resident peritoneal macrophages and thioglycollate-elicited macrophages. Whereas resident cells showed no detectable activity, inflammatory macrophages and monocytes both bound transferrin to a similar degree. The calculated dissociation constant (2.3 X 10(-10)) and the number of sites per monocyte (11,400) compared favorably with those reported for transferrin receptors on inflammatory macrophages. Thus, based on the expression of the transferrin receptor, murine monocytes resemble murine inflammatory peritoneal macrophages rather than resident tissue macrophages.

Animals↗
PubMed1984

Studies of immune function and host resistance in B6C3F1 mice exposed to formaldehyde.

A series of immune function and host resistance parameters were examined in female B6C3F1 mice following a 21-day (6 hr/day) inhalation exposure to 15 ppm of formaldehyde (HCHO). Immune parameters examined included delayed hypersensitivity to keyhole limpet hemocyanin, antibody plaque-forming cell response to sheep erythrocytes (T-lymphocyte-dependent antigen) and TNP-Ficoll (T-lymphocyte-independent antigen), lymphoid organ weights and histopathology, routine hematology, bone marrow cellularity and CFU progenitor cell enumeration, lymphocyte subpopulation quantitation by cell surface markers, mitogen-induced lymphocyte blastogenesis, macrophage function parameters, and host resistance to challenge with the bacterium Listeria monocytogenes and transplantable tumor cells. Lymphoid organ weight, bone marrow cellularity, and hematology parameters were unchanged in HCHO exposed mice. Similarly, the percentage of T and B lymphocytes and their proliferative responses to mitogens were not significantly altered. Antibody (IgM) plaque-forming cell response following antigen challenge was unchanged. Macrophage function was normal although some evidence of enhanced H2O2 production associated with elevated bactericidal activity was observed in resident macrophages. Resistance to challenge with the bacteria Listeria monocytogenes was significantly enhanced, while resistance to tumor challenge remained unchanged. No evidence of immunosuppression following short-term exposure to HCHO was observed.

Animals↗
PubMed1984

Antibody-dependent cytolysis (ADCC) of tumor cells by activated murine macrophages is a two-step process: quantification of target binding and subsequent target lysis.

To analyze the antibody-dependent cell-mediated cytotoxicity (ADCC) reaction between tumor cells and activated murine macrophages in detail, it must be first determined if physical binding occurred between the two cell types. Over 15-20 min in vitro, antibody-coated HSB neoplastic targets became so firmly attached to the activated macrophages that they resisted removal with 4 vigorous washes. When a quantitative assay of binding was employed, attachment of tumor cells to activated macrophages was found to depend on the concentration of antibody and on the density of the macrophages. These two variables also determined the subsequent extent of cytolysis. Binding of antibody-coated targets by macrophages elicited with thioglycollate broth or activated by bacillus Calmette-Guerin (BCG) was comparable. Lysis by the activated macrophages, however, was far greater. Binding occurred at 4, 22, or 37 degrees C, while the subsequent lytic reaction occurred only at 37 degrees C. Thioglycollate broth effectively inhibited lysis but had no effect on binding. A porous filter placed between activated macrophages and targets resulted in abrogation of binding and lysis, even when antibody-coated targets were placed beneath the filters. When labeled, uncoated targets were added to cultures of macrophages in the presence of unlabeled antibody-coated targets, no lysis of the bystander (i.e., uncoated) targets was seen. The data suggest that ADCC is a multistep reaction, that vigorous physical binding of antibody-coated targets by activated macrophages is an initial and necessary step in ADCC, that such binding is not sufficient for ADCC, that such binding controls the selectivity of lysis in ADCC, and that the second step in ADCC results in target lysis.

Animals↗
PubMed1984

Expression of the transferrin receptor on murine peritoneal macrophages is modulated by in vitro treatment with interferon gamma.

The expression of transferrin receptors on murine peritoneal macrophages has been shown to be down regulated during functional activation in vivo. This observation suggested that the level of transferrin receptor expression varies in response to discrete extracellular signals known to induce macrophage activation. We have tested this concept directly and have shown that decreased transferrin receptor expression can be reproduced in vitro by treatment of inflammatory macrophages with preparations of interferon gamma derived from a T cell hybridoma supernatant. The ability of this agent to down regulate the expression of the transferrin receptor exhibited dose and time dependencies similar to those required for development of other macrophage functions in vitro. The addition of LPS produced no further decrease in receptor expression. Furthermore, murine gamma interferon, produced by recombinant DNA technology also caused a downshift in transferrin receptor expression at doses similar to those which have been shown previously to induce activation. The changes in receptor activity were the result of altered numbers of binding sites and the receptor:ligand affinity remained unaffected. These results indicate that altered expression of the transferrin receptor is one element of the pleiotypic change which macrophages undergo in response to IFN gamma. This system may, therefore, provide a useful model in which to study the biochemical basis of IFN gamma action in mononuclear phagocytes.

Animals↗
PubMed1984

Tumors undergoing rejection induced by monoclonal antibodies of the IgG2a isotype contain increased numbers of macrophages activated for a distinctive form of antibody-dependent cytolysis.

Monoclonal antibodies of the IgG2a isotype specifically inhibit the growth of human tumors in nude mice; tumors in mice given no antibody, an antibody of the IgG2a isotype that does bind to the tumor cells, or an antibody of the IgG2b isotype grow progressively. In the present work it is demonstrated that tumors of mice given the IgG2a antibody are essentially masses of necrosis, while tumors from the control mice are sheets of healthy tumor cells. Tumors of the treated mice, in comparison to controls, contain an increased number of macrophages, and these macrophages are activated for a distinct form of cytolysis dependent on antibodies of the IgG2a isotype. The data suggest that changes in the number and function of intratumoral macrophages are a major component of tumor destruction mediated by IgG2a antibodies.

Animals↗
PubMed1984

Expression of the transferrin receptor in murine peritoneal macrophages is modulated in the different stages of activation.

A specific high affinity binding site for the serum glycoprotein transferrin was identified on murine peritoneal macrophages. The binding reached equilibrium within 60 min and was reversible, saturable, and specific for transferrin. Although the presence of this receptor was detected on the cell surface by studies carried out using intact cells, the majority (70 to 90%) of the binding activity was detectable only in detergent extracts of such cells. This suggests that a substantial portion of the binding activity is localized within the macrophage. The association constant (Ka) for binding to intact cells (6 to 9 X 10(8) M-1) was comparable to values reported for transferrin receptors described on other cell types. The expression of transferrin binding activity was examined in macrophages exhibiting qualitatively and quantitatively different degrees of functional activation. Resident peritoneal macrophages, exudate macrophages primed by elicitation with pyran copolymer, and activated macrophages induced by chronic infection of mice with bacillus Calmette-Guerin (BCG) or elicitation with heat killed Propionibacterium acnes (P. acnes) had low numbers of binding sites (1000 to 5000 total sites/cell). Macrophages elicited by sterile inflammatory agents (thioglycollate broth, fetal bovine serum, or casein) all exhibited a greater number of transferrin receptors (15,000 to 20,000 total sites/cell). This modulation did not appear to result from differential shifts between surface and internal loci. Our results suggest that the expression of the transferrin receptor may be a useful marker of the responsive stage of macrophage functional activation and the membrane changes that accompany activation.

Animals↗
PubMed1983

Sequential activation of murine mononuclear phagocytes for tumor cytolysis: differential expression of markers by macrophages in the several stages of development.

Murine mononuclear phagocytes in various stages of activation were elicited in vivo or induced in vitro. The cytolytic competence of each type of macrophage, before and after treatment with traces of endotoxin, was quantified. Populations of responsive, primed, and activated macrophages, but not resident macrophages, expressed five markers that have been reported to characterize inflammatory macrophages: increased spreading, increased phagocytosis via Fc and C3 receptors, increased secretion of plasminogen activator, and decreased content of the ectoenzyme 5' nucleotidase. Primed macrophages secreted cytolytic protease (CP) when pulsed with traces of endotoxin; the resident and responsive macrophages did not. The primed macrophages bound tumor cells to a considerable degree; the resident and responsive macrophages did not. The cytolytically activated macrophages bound tumor cells well and secreted lytic protease spontaneously. The capacity for augmented, selective binding of tumor cells is apparently induced in only one step by application of lymphokine(s). The capacity for secreting CP, however, is regulated in two steps; initial priming signals--lymphokine(s)--prepare the macrophages for secretion, and a second signal, such as endotoxin or endotoxin plus tumor cells, triggers the actual release of CP.

5'-Nucleotidase↗
PubMed1983

The binding of tumor cells by murine mononuclear phagocytes can be divided into two qualitatively distinct types.

Peritoneal macrophages from C57BL/6N mice infected with BCG have a greater capacity for tumor cell binding than do inflammatory macrophages elicited by several agents. To determine if these quantitatively distinct types of binding were qualitatively distinct as well, we compared them in several ways. Scanning electron microscopy of macrophage-tumor cell interactions reveals clustering of 2 to 5 tumor targets on the central portion of BCG-activated macrophages, in contrast to the very few tumor cells found at the periphery of inflammatory macrophages. Tumor cell binding to BCG-activated macrophages required divalent cations and trypsin-sensitive surface structures on the macrophages, but the low-level binding to inflammatory macrophages required neither. The ability of trypsinized BCG-activated macrophages to bind P815 tumor targets was recovered with time in culture. BCG-activated macrophages required intact energy metabolism, microfilaments, and microtubules to complete augmented tumor cell binding, whereas inflammatory macrophages did not. Targets bound to BCG macrophages could be competitively removed by addition of large excesses of unlabeled tumor cells, but targets bound to inflammatory macrophages could not be so removed. Tumor cells labeled with 111Indium oxine were used to estimate the specific (i.e., competitively inhibitable) and nonspecific (noncompetitively inhibitable) components of binding. Binding of P815 tumor cells to BCG-activated macrophages was predominantly specific, whereas their binding to inflammatory macrophages was predominantly nonspecific. Binding by activated or inflammatory macrophages of lymphocytes or by transformed 3T3 cells of neoplastic or non-neoplastic targets was also nonspecific. Binding by BCG-elicited macrophages from A/J mice, previously demonstrated to be quantitatively deficient in binding ability, was qualitatively similar to that to inflammatory macrophages and was not competitively inhibitable. The data suggest that tumor cell binding by activated macrophages is qualitatively as well as quantitatively distinct from binding to inflammatory macrophages.

Animals↗
PubMed1983

Effect of pyran copolymer on activation of murine macrophages: evidence for incomplete activation by use of functional markers.

The degree of activation of peritoneal macrophages elicited by pyran copolymer (MVE-2) was studied in C57BL/6J mice. When cytotoxicity was examined under endotoxin-free culture conditions, the pyran-elicited macrophages could not complete cytolysis of tumor target cells. The macrophages, however, completed cytolysis when pulsed with endotoxin. These results were obtained when either the interval between injection of the pyran copolymer and harvest of the macrophage or the dose of pyran was varied. The pyran-elicited macrophages expressed five markers considered to be typical of inflammatory macrophages, and bound tumor cells to an augmented degree. The pyran-elicited macrophages were capable of secreting a potent cytolytic proteinase when pulsed with endotoxin, but did not secrete cytolytic proteinase spontaneously. The pyran-elicited macrophages, in contrast to inflammatory macrophages, could effect cytostasis of tumor cells; their cytostatic potential was also augmented by addition of endotoxin. Taken together, the results indicated that pyran copolymer elicits primed but not fully activated murine macrophages.

Animals↗
PubMed1982

Receptors for maleylated proteins regulate secretion of neutral proteases by murine macrophages.

Receptors for maleylated or acetylated proteins as well as for alpha-2-macroglobulin-protease complexes on macrophages serve as scavengers by mediating the uptake of macromolecules from the extracellular compartment. Described in this report is a novel function of these receptors on macrophages: regulation of neutral protease secretion. The binding of maleylated bovine serum albumin to macrophages triggered secretion of three neutral proteases: neutral caseinases, plasminogen activator, and cytolytic proteinase. Release of acid phosphatase, however, was not induced. An important biological consequence of protease secretion by macrophages, tumor-cytolysis, was also triggered by engagement of the receptor for maleylated bovine serum albumin. By contrast, the binding of alpha-2-macroglobulin-protease complexes to the macrophages suppressed secretion of all three proteases. Thus two receptors heretofore believed to serve principally as scavengers also regulate secretory functions of macrophages.

Animals↗
PubMed1982

Incidence and nature of primary granulomatous inflammation in surgically removed material.

A large number of cases (303) of primary granulomatous inflammation, present in surgically removed specimens from a broad range of locations, were reviewed and examined in detail. The granulomas were characterized as to morphology, location, and etiology. Epithelioid granulomas without necrosis were most frequently due to sarcoidosis and mycobacterial infection, while epithelioid granulomas with necrosis were most commonly due to mycobacterial infection, fungal infection, rheumatoid arthritis and sarcoidosis. Mature granulomas, most of which did not contain necrosis, were generally due to foreign bodies. The responsible etiologic agents were generally identified in granulomas due to fungi, bacteria, or foreign bodies (92%). However, mycobacteria were infrequently identified in granulomas, even when the lesions were examined by the auramine-O technique (31%). Overall, the majority of the granulomas (76%), were due to five causes: sarcoidosis, mycobacterial infection, particulate inclusions, fungal infection, and rheumatoid arthritis. The frequency of a given etiology, however, varied widely depending on the location of the lesion. By classifying granulomas morphologically and knowing their location, useful predictive information concerning the etiology of a given granuloma, beyond that obtained by histochemical stains, could be derived.

Granuloma↗
PubMed1982

Biosynthesis of ethylene from methionine in aminoethoxyvinylglycine-resistant avocado tissue.

This study was conducted to determine if aminoethoxyvinylglycine (AVG) insensitivity in avocado (Persea americana Mill., Lula, Haas, and Bacon) tissue was due to an alternate pathway of ethylene biosynthesis from methionine. AVG, at 0.1 millimolar, had little or no inhibitory effect on either total ethylene production or [(14)C] ethylene production from [(14)C]methionine in avocado tissue at various stages of ripening. However, aminoxyacetic acid (AOA), which inhibits 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (the AVG-sensitive enzyme of ethylene biosynthesis), inhibited ethylene production in avocado tissue. Total ethylene production was stimulated, and [(14)C]ethylene production from [(14)C]methionine was lowered by treating avocado tissue with 1 millimolar ACC. An inhibitor of methionine adenosyltransferase (EC 2.5.1.6), l-2-amino-4-hexynoic acid (AHA), at 1.5 millimolar, effectively inhibited [(14)C]ethylene production from [(14)C]methionine in avocado tissue but had no effect on total ethylene production during a 2-hour incubation. Rates of [(14)C]AVG uptake by avocado and apple (Malus domestica Borkh., Golden Delicious) tissues were similar, and [(14)C]AVG was the only radioactive compound in alcohol-soluble fractions of the tissues. Hence, AVG-insensitivity in avocado tissue does not appear to be due to lack of uptake or to metabolism of AVG by avocado tissue. ACC synthase activity in extracts of avocado tissue was strongly inhibited (about 60%) by 10 micromolar AVG. Insensitivity of ethylene production in avocado tissue to AVG may be due to inaccessibility of ACC synthase to AVG. AVG-resistance in the avocado system is, therefore, different from that of early climacteric apple tissue, in which AVG-insensitivity of total ethylene production appears to be due to a high level of endogenous ACC relative to its rate of conversion to ethylene. However, the sensitivity of the avocado system to AOA and AHA, dilution of labeled ethylene production by ACC, and stimulation of total ethylene production by ACC provide evidence for the methionine --> SAM --> ACC --> ethylene pathway in avocado and do not suggest the operation of an alternate pathway.

Journal Article↗