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Biomedical subjects

N Hogg

Publications and source records attributed to N Hogg.

195 records · Page 11Linked to original sources

Monoclonal antibody with specificity for monocytes and neurons.

We have characterized a monoclonal antibody, called UC45, that reacts with both monocytes and neurons. It was derived from a fusion of the NS-1 plasmacytoma cell line with spleen cells from a mouse immunized with human acute monoblastic leukemia cells. The antibody reacts weakly with viable monocytes in suspension but has specificity for fibrous projections, which are found on monocytes that have adhered to substrate. Other hemopoietically derived cells such as granulocytes and lymphocytes, and many tissue-culture lines, do not react with UC45 by cell-surface immunofluorescence. Similarly, UC45 reacts with the processes of both viable CNS and PNS neurons in tissue culture but with no other neural-tissue-derived cells. The monoclonal antibody has interspecies reactivity, in that it reacts with human, rat and mouse monocytes and neurons. The monocytes and neuronal antigen is present predominantly on a protein of 45 kd. Attempts to identify this protein on monocytes with conventional heteroantisera directed against fibronectin, complement components, fibrinogen, collagen, tubulin and actin have failed. A monoclonal antibody has therefore allowed identification of an antigen, unexpectedly shared by monocytes and neurons. The fact that it is found on cell processes of both cell types suggests that it may be performing some similar function for these cells, whose other activities differ substantially.

Animals↗

Species restriction in cytostatic activity of human and murine monocytes and macrophages.

The pattern of species restriction in cytostatic activity of human breast-milk macrophages (Mph) and murine starch-activated peritoneal exudate (PE) Mph was investigated. Human Mph had appreciable cytostatic activity only for human target cells and not for murine or avian target cells. In contrast, murine Mph were particularly cytostatic for target cells from heterologous species and not as cytostatic for other murine cells. This difference in the activity of murine Mph was more notable when freshly explanted fibroblasts were used as target cells than when the cytostasis of long-term tissue culture lines was measured. Experiments with peripheral blood monocytes from the two species indicated that this pattern of reactivity may be common to mononuclear phagocytes from other sources. Therefore, human Mph are preferentially cytostatic for target cells of self species; whereas, murine Mph are equally if not more cytostatic for target cells from other species.

Animals↗

Lack of Fc receptors on osteoclasts.

Fc and C3 receptors, which are characteristically present on macrophages, could not be demonstrated on osteoclasts maintained in situ on their normal substrates when assayed for by use of sheep red blood cells coated with immunoglobulin (Shapiro et al. 1979). The present study tested the hypotheses that Fc receptors are present only on the osteoclast surface adjacent to bone and that Fc receptors on osteoclasts can be uncovered by enzymes or stimulated to appear. Freeze-dried, inverted osteoclasts (and osteoblasts) obtained from the endocranium of newborn rats were tested for Fc receptors using the rosette assay and examined by scanning electron microscopy. No rosettes were observed on the surfaces of the osteoclasts that had been approximal to the bone. Bone specimens were cultured for 30 min at 37 degrees C in control medium, or in medium with the addition of 10, 50 or 100 microgram/ml trypsin, 0.5 U/ml parathyroid extract (PTE), or 0.5 or IU/ml parathyroid hormone 1--34 (PTH). Additionally, two week-old rats were injected intraperitoneally with PTE (1.5 U/g body weight or 1 USP/g body weight) or with PTH (1 U/g body weight) or with vehicle alone, 6 h before sacrifice. The specimens were assayed for Fc receptors and examined by scanning electron microscopy. Macrophages were always used as controls for the assay. No rosettes were present on osteoclasts subjected to any of these treatments. Accordingly, the hypotheses were not supported.

Animals↗

Surface antigens of the murine cytostatic peritoneal macrophage.

By rosetting techniques, peritoneal exudate cells (PEC) from mice stimulated intraperitoneally with starch have been shown to be a mixed population of cells consisting of the following subpopulations of cells: 75% FcR, 26% C3R, 18% Ig+, 29% Ia+, Ig- and 5% Thy-1+, Ig-. By separating rosetting from non-rosetting cells, it was possible to establish the phenotype of the PEC which was cytostatic for tumour cells. This cell possessed receptors for Fc and C3 but lacked surface Ig, the Thy-1 antigen and I-region controlled antigens and was NSE positive. Thus by presently available criteria, the cytostatic PEC can be identified as a macrophage. The lack of Ia distinguishes this type of macrophage from the antigen-presenting macrophage which bears Ia.

Animals↗

Characterization of human breast milk macrophages cytostatic for human cell lines.

Approximately 40% of the cells in human early lactation milk possessed the characteristics of macrophages, being adherent, phagocytic, alpha napthyl acetate esterase positive, and possessing C3b and Fc receptors. These cells were also cytostatic for MDA 157, a cell line derived from a pleural effusion of human breast cancer, and HEL 23, a strain of human fetal lung fibroblasts. Investigations into the cytostatic phenomenon indicated that the cytostasis could not be mediated by macrophage-conditioned medium and that very close contact between breast milk macrophages and target cells was required. Cytostasis was not fully effective until 18 hr after the initial interaction between macrophages and target cells.

Breast↗

Gross-virus-induced lymphoma in the rat. IV. Cytotoxic cells in normal rats.

Lymphoid cells from normal W/Fu rats are cytotoxic in vitro for syngeneic Gross-virus-induced lymphoma cells in a 4 1/2 h 51Cr release test, and protect against tumour growth in vivo when adoptively transferred to syngeneic recipient rats. Cytotoxicity by normal lymphoid cells was greater with in vitro rather than in vivo passaged target cells, and was increased by preincubation of the lymphoid cells at 37 degrees C for 3 h in vitro before their addition to the target cells. Cytotoxic activity, which was localized predominantly in the spleen, was absent at birth but increased until adulthood with some decline in older age. Histocompatibility at the major Ag-B locus was not required for the killer cell--target cell interaction; normal spleen cells of many Ag-B genotypes were cytotoxic for W/FuG-1 target cells, although BDIX and (BDIX X W/Fu)F1 were less active and BN were inactive. The specificity of cytotoxicity was studied by the techniques of direct lysis, competitive inhibition or adsorption to cellular monolayers, using a variety of cell lines. Selectively of lysis or binding was observed and was restricted to rat target cells releasing exogenous or endogenous C-type viruses.

AKR murine leukemia virus↗

Role of macrophages in the generation of T helper cells. IV. Nature of genetically related factor derived from macrophages incubated with soluble antigens.

Macrophages incubated with soluble antigens for 1-4 days release factors capable of inducing T helper cells. The nature and some of the properties of this genetically related macrophage factor (GRF) were investigated. By use of immunoadsorbents, GRF was shown to contain I region-coded products (Ia antigens) linked to a small antigenic fragment. The genes coding for the Ia antigens detectable in GRF lie in the I region of the H-2 complex. GRF does not react with anti-immunoglobulin, anti-C3 or anti-human beta2-microglobulin antisera, and its activity cannot be removed by antigen immunoadsorbents. GRF is heat-labile, sensitive to proteolytic enzymes and has a molecular weight of about 55 000 Daltons. The relationship of GRF to other factors known to contain I region-coded products and reported to be effective in cell cooperation is discussed.

Animals↗

The antioxidant effect of spermine NONOate in human low-density lipoprotein.

The nitric oxide (*NO) donor N-[4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl]-1,3- propanediamine, also referred to as Spermine NONOate (SNN), inhibited the copper(II) sulfate-initiated oxidative modification of human low-density lipoprotein (LDL) as measured by the formation of thiobarbituric acid reactive substances, conjugated diene formation, and changes in electrophoretic mobility. The presence of the nitronyl nitroxide 1-oxy-2-[p-(trimethylammoniumyl)phenyl]-4,4,5,5- tetramethylimadazoline 3-oxide, a scavenger of *NO, antagonized the inhibitory activity of SNN. The inhibition of copper-dependent LDL oxidation had a nonlinear dependence on SNN concentration. Low concentrations of SNN ( < 4 microM) were only poorly effective at inhibiting LDL oxidation; however, a dramatic enhancement of inhibition occurred above 4 microM SNN. This behavior was qualitatively different from that of butylated hydroxytoluene, a phenolic chain-breaking antioxidant, which exhibited an approximately linear concentration dependence in this system. Addition of 13[S-(E,Z)]-hydroperoxy-9,11-octadecadienoic acid, a lipid hydroperoxide, to LDL diminished the antioxidant effect of 4 and 8 microM SNN, but not that of 12 microM SNN. SNN inhibited the depletion of alpha-tocopherol during both copper-dependent and 2,2'-azobis(2-amidinopropane)-dependent oxidation of LDL. We propose that a direct reaction is occurring between NO and the lipid peroxyl radical, forming a lipid-nitroso adduct. Formation of this product would not only remove the lipid peroxyl radical, thus preventing chain propagation, but would also prohibit the regeneration of lipid hydroperoxide, thereby stopping further transition metal ion-dependent initiation. The difference in the kinetic behavior between SNN and conventional antioxidants can be explained by this effect.

Amidines↗