Vena caval pressure gradients during liver transplantation.
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Blood Pressure↗
Biomedical subjects
R Peck
Publications and source records attributed to R Peck.
Gamma interferon induces monocyte killing of Listeria monocytogenes by an oxygen-dependent pathway; alpha- or beta-interferons by oxygen-independent pathways.
Human peripheral blood monocytes purified by counterflow centrifugal elutriation were treated with recombinant interferons-gamma (IFN-gamma), alpha (IFN-alpha), or beta (IFN-beta)--and tested for their capacity to kill Listeria monocytogenes. All three IFNs increased the monocyte bactericidal activity in a dose-dependent fashion. Exogeneous catalase, an inhibitor of monocyte-generated hydrogen peroxide, did not affect bactericidal activity. However, exogenous superoxide dismutase inhibited killing by IFN-gamma-activated monocytes, but not by IFN-alpha- or IFN-beta-activated monocytes. By contrast, exogenous soybean trypsin inhibitor inhibited killing by IFN-alpha or IFN-beta-activated monocytes, but not by IFN-gamma-activated monocytes. Combinations of IFN-gamma and IFN-alpha resulted in no increase in bactericidal activity. Finally, treatment with IFN-gamma resulted in different receptiveness of the cell to subsequent oxidative burst-stimulating signals than did treatment with either IFN-alpha or IFN-beta. These results suggest that monocytes treated with IFN-gamma kill L. monocytogenes by an oxygen-dependent mechanism, but treatment with IFN-alpha or IFN-beta elicits principally oxygen-independent mechanisms.
Blood Bactericidal Activity↗
Cell surface tumor necrosis factor (TNF) accounts for monocyte- and lymphocyte-mediated killing of TNF-resistant target cells.
WEHI164 cells are susceptible to cytotoxicity by soluble recombinant or monocyte-derived TNF alpha, as well as to cell-mediated cytotoxicity by monocytes or lymphocytes. In contrast, K562 cells are resistant to lysis by soluble recombinant or natural TNF alpha, but are killed by monocyte or lymphocyte effector cells. Cell-mediated cytotoxicity against both target cell lines is enhanced by treatment of monocyte effector cells with recombinant interferon gamma or lymphocyte effector cells with interleukin-2. However, treatment of monocytes with LPS, or of lymphocytes with PHA, although inducing secretion of soluble TNF alpha in the medium, does not increase cell-mediated cytotoxicity. Anti-TNF alpha neutralizing antibodies partially inhibit monocyte- as well as lymphocyte-mediated cytotoxicity against WEHI164 and K562 cells. Formaldehyde-fixed effector cells are cytotoxic to both target cell lines. Cytotoxicity by fixed effector cells can be inhibited by anti-TNF alpha antibodies. The extent of cell-mediated cytotoxicity induced by treatment of effector cells with stimulators prior to fixation corresponds to the expression of TNF on monocyte membranes, but not to the titers of secreted TNF. The data suggest that membrane-associated TNF alpha may be a mechanism of human monocyte- as well as lymphocyte-mediated cytotoxicity, regardless of whether the target cells are sensitive or insensitive to soluble TNF.
Animals↗
Nerve growth factor induces growth and differentiation of human B lymphocytes.
Nerve growth factor (NGF) is known to affect peripheral sympathetic and sensory neurons as well as defined populations of neurons in the central nervous system. This paper presents evidence that NGF is also active in modulation of B-cell-mediated immune responses. NGF receptors were immunoprecipitated from highly purified human B-cell populations, and to a lesser extent, from T-cell populations, by using a monoclonal antibody recognizing NGF receptors present on neural cells. NGF receptors were also detected in significant amounts in human spleen and lymph node tissue. In addition, NGF induced a dose-dependent increase in B-cell DNA synthesis as determined by incorporation of [3H]thymidine. This B-cell growth-promoting activity was inhibited by a neutralizing anti-NGF monoclonal antibody. Immunoglobulin secretion, principally affecting IgM synthesis, was also modulated by NGF. The concentrations that affected B-cell proliferation are consistent with the presence of functional high-affinity NGF receptors. The results suggest that NGF, in addition to its neurotrophic function, also acts as an immunoregulatory cytokine.
Antibodies, Monoclonal↗
Persistent high fever and gall-bladder wall thickening in a child with primary Epstein-Barr viral infection.
A 3.5 year old girl presented with a history of high fever, rigors, and mild cough for 1 week. Physical examination revealed normal chest findings but gross hepatomegaly was detected. Liver function tests were abnormal and indicated biliary obstruction. Ultrasonography revealed a distended gall-bladder with increased wall thickness up to 0.6 cm. The diagnosis of primary Epstein-Barr viral infection was eventually made by specific serological study. The patient's fever subsided 2 weeks later and her liver function tests returned to normal 1 month later. Abdominal ultrasonography at this time was normal.
Acute Disease↗
Immunocytochemical studies on the basal ganglia and substantia nigra in Parkinson's disease and Huntington's chorea.
The basal ganglia and substantia nigra, taken from control human brain and from patients dying with a diagnosis of Parkinson's disease or Huntington's chorea, were analysed with histochemical and biochemical techniques. The pigmented neurons of the substantia nigra pars compacta possess tyrosine hydroxylase immunoreactivity and are disposed in three major layers, alpha, beta and gamma. This pattern became obscured in choreic brains by the severe shrinkage of the nigra, but total numbers of pigmented neurons were within the normal range. In contrast, pigmented neurons were lost from all layers of the substantia nigra in Parkinson's disease, although examination of cases with minimal cell loss suggested that an internal part of the lateral alpha sub-layer was most severely and consistently affected. A dopaminergic projection between this internal part of the alpha sub-layer and the putamen was suggested by the preferential loss of catecholamines from the putamen in Parkinson's disease. The distribution of the peptides, substance P, methionine-enkephalin and dynorphin 1-17 were mapped immunohistochemically within the substantia nigra. The different patterns of immunoreactive axons and terminals were found to be extensive, at least partially overlapping, and largely avoided the region of the pigmented perikarya of the alpha sub-layer and nucleus paranigralis. All peptides were depleted in choreic substantia nigra, reflecting the degeneration of the striatonigral pathway. However, concentrations of enkephalin-like immunoreactivity were increased within the interpeduncular nucleus. In Parkinson's disease there was a loss of enkephalin- and dynorphin-like immunoreactivity from the substantia nigra but a fall in substance P-like immunoreactivity was only detected by radioimmunoassay, not by immunocytochemistry. Peptide immunoreactivity was also reduced within choreic basal ganglia. However, no gross changes were found in peptide staining of the parkinsonian basal ganglia. In summary we have reported a number of changes in peptide-containing pathways in human degenerative disorders that may reflect the degeneration of neuronal pathways either as a primary event or secondary to initial lesion. We have also emphasized the sensitivity of the alpha sub-layer of nigral neurons to damage in Parkinson's disease. We suggest that the lower density of peptidergic fibres in the area of the perikarya may contribute to the susceptibility of these neurons to damage.
Adult↗
Acute and chronic undernutrition in Swaziland.
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Child, Preschool↗
Neuropeptides modulating macrophage function.
The immune system and the neuroendocrine system affect each other via molecules and receptors shared by both systems. Neuroendocrine hormones may act either positively or negatively in regulating the activities of a key cell of the immune system, the macrophage. For example, adenocorticotropic hormone (ACTH), somatostatin, and substance P are all capable of increasing the cytotoxicity of macrophages against tumor cells. However, ACTH and somatostatin, but not substance P, can also block the tumoricidal activity of macrophages induced by recombinant gamma interferon (IFN-gamma), a non-neuroendocrine immunomodulating hormone. In contrast, substance P increased tumoricidal activity, both independent of IFN-gamma and in addition to IFN-gamma. Neurotensin, alpha-endorphin, beta-endorphin, met-enkephalin, vasopressin, and substance K did not affect tumoricidal function, either alone or in combination with IFN-gamma. Substance P, but not the other neuropeptides, increased substantially the proportion of macrophages able to secrete superoxide ions, suggesting a possible influence on macrophage capacity to deal with microbial infection. Such positive and negative modulation of macrophage effector functions could contribute to the influence of cognitive stimuli in infection and neoplasia.
Adjuvants, Immunologic↗
Recombinant interferons or interleukin-2 increase cytotoxicity by human monocytes and NK cells.
Human peripheral blood monocytes and NK cell enriched lymphocytes were purified by counterflow centrifugal elutriation. The cell populations were characterized by surface marker analysis using monoclonal antibodies. A variety of molecules were found to be capable of activating monocytes and NK cells to enhanced tumoricidal activity. Tumoricidal activity was evaluated using a colorimetric microassay. Numbers of tumor cell targets surviving exposure to monocytes or NK cells were calculated by computer analysis of colorimetric data derived by target cell-dependent dye reduction. The results indicated that monocyte effector cells were cytotoxic to the NK sensitive K562 cell line and to the monocyte sensitive TU5 line. Depletion of NK contaminants from the monocyte population by complement mediated cytolysis did not affect the capacity of the monocytes to kill either target. Monocyte mediated cytotoxicity was enhanced by treatment of the monocytes with recombinant IFN-alpha, IFN-beta, or IFN-tau; each in a dose-dependent manner. Simultaneous treatment of monocytes with IFN-alpha and IFN-tau resulted in additive but not synergistic effects. NK cell cytotoxicity was enhanced by treatment with IL-2 or IFN-tau. Enhancement of monocyte and NK cell cytotoxicity by IFN or IL-2 was dependent upon the time in culture of the effector cells, the duration of the effector phase, and the effector to target cell ratio. IFN or IL-2 treatment alone did not reduce target cell viability. The results suggest that monocytes as well as NK cells are capable of providing a natural defence against neoplasia, that monocytes can kill NK targets and NK cells can kill monocyte targets, and that these cytotoxic activities are enhanced by IFN or IL-2.
Cell Line↗
An assay for macrophage activating factor based on the adherence of oil-elicited guinea pig macrophages: characterization of a lymphokine-induced release of hydrogen peroxide from elicited macrophages.
A convenient procedure is described for assaying guinea pig macrophage activating factor (MAF) in lymphokine preparations. The assay utilizes oil-elicited peritoneal macrophages from strain 2 guinea pigs and measures the capacity of macrophage cultures pretreated with lymphokine or medium to release hydrogen peroxide (H2O2) in the presence and absence of phorbol myristate acetate (PMA). The PMA-induced release measures a maintenance of macrophage adherence and activation. A novel aspect is a lymphokine-dependent release of H2O2 which occurs in the absence of PMA and which differs from the PMA triggered release. The differentiation process into lymphokine responsive cells has been studied using macrophages elicited from 2-21 days after oil injection. In addition macrophage responsiveness was examined in different strains of guinea pigs.
Animals↗
A one-plate assay for macrophage bactericidal activity.
Human peripheral blood monocytes purified by counterflow centrifugal elutriation (CCE) showed an enhanced capacity to kill Listeria Monocytogenes and Staphylococcus aureus after activation with interferon-gamma (IFN gamma). Bactericidal activity was evaluated by a rapid colorimetric microassay based on the reduction of a tetrazolium dye, MTT. The amount of dye reduced was directly proportional to the number of viable bacteria present in each microwell. Comparison with a bacterial titration plate containing serial dilutions from stock of a known titer allowed calculation of bacterial numbers before and after exposure to macrophages. Results were read in a multiscan plate reader and compared closely with those obtained by serial dilution on agar plates (i.e., colony counts). The entire assay, i.e., culturing the monocytes, treatment with IFN gamma, addition of the bacteria, and quantitation of surviving viable bacteria, was performed in a single microtiter plate.
Blood Bactericidal Activity↗
Production and characterization of antisera against guinea pig macrophage activating factor.
Guinea pig lymph node cells stimulated with concanavalin A (Con-A) were used as a source of lymphokines. Purifications by molecular sizing columns yielded sufficient quantities of macrophage activating factor (MAF)-active fractions to allow immunization of rabbits. An antiserum was produced which is capable of specifically inhibiting MAF activity, as well as blocking the activity of macrophage migration inhibiting factor (MIF), but not of skin reactive factor. Antisera raised against control supernatants derived from lymph node cells not stimulated with Con-A, failed to specifically inhibit any of these lymphokines. Additionally, anti-MAF but not anti-control antibodies suppressed completely contact sensitivity to dinitrochlorobenzene.
Animals↗
An ELISA method for quantitation of macrophage migration from agarose microdroplets.
A method is described for quantitating the biological activity of macrophage migration inhibitory factor (MIF) based on the detection of macrophages migrating from agarose droplets. The migration is determined with polyclonal anti-macrophage antibodies in an ELISA assay. The numbers of macrophages thus detected correlate well with the migration as measured by a capillary tube assay for MIF.
Animals↗
Origin of peripheral blood macrophages in bursa-cell-reconstituted chickens. Further evidence of MHC-restricted interactions between T and B lymphocytes.
MHC class-I antigens on peripheral blood macrophages and bursa cells were analysed after adoptive bursa cell transfer to cyclophosphamide-treated immunodeficient chickens. We studied the expression of B-F locus-encoded antigens (B-F is homologous to mouse H-2K, D) on macrophages and B cells and found that macrophage B-F antigens are of host origin, whereas bursa cells express only donor-type B-F antigens. Both syngeneic and allogeneic bursa cells restored IgM antibody production to a T-cell-independent antigen, Brucella, but only syngeneic bursa cells could restore the IgG antibody response to a thymus-dependent antigen, sheep erythrocytes. The results indicate that B-cell maturation and macrophage-B-cell interaction are not MHC-restricted but that a restriction exists in T-cell-B-cell collaboration.
Animals↗
The effects of cyclosporin A on the chicken immune system.
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Administration, Oral↗
Expression of B-L (Ia-like) antigens on macrophages from chicken lymphoid organs.
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Animals↗
Adoptive transfer of cross-protection among alphaviruses in mice requires allogeneic stimulation.
Cell-mediated (T-effector cell) immunity is proposed as playing the major role in cross-protection between Sindbis and Semliki Forest viruses, which are alphaviruses that do not elicit cross-neutralizing antibodies. In adoptive transfer experiments, T-cells from spleens of Sindbis virus-immunized mice were found to confer specific cross-protection to Semliki Forest virus upon recipient mice. This cross-protection was observed in the outbred ICR strain of mice and when transfers were made between several combinations of inbred and hybrid strains. Cross-protection was substantially reduced if syngeneic rather than allogeneic cell transfers of one spleen equivalent per mouse were made. The results suggest that allogeneic stimulation (mixed lymphocyte reaction in vivo) is necessary to increase the number of effector cells (donor) in the recipient. This was supported by the observation that blastogenic stimulation of donor cells in vitro by concanavalin A induces cross-protection in syngeneic animals. Conversion of recipient cells to specific effector cells also appears to play a role in protecting mice against Semliki Forest virus. This was concluded from the experiments described above, a time course study, and the results of experiments that involved serial passages of transferred cells across histocompatibility barriers. Thus, we propose that both donor and recipient cells are active in protecting recipient mice against challenge with Semliki Forest virus after adoptive transfer.
Animals↗
In vitro heterologous cytotoxicity by T effector cells from mice immunized with Sindbis virus.
An in vitro correlate of cell-mediated cross-protection among alpha-viruses was demonstrated by cytotoxicity of Sindbis-immune spleen cells from mice to both Sindbis and Semliki Forest virus (SFV)-infected target cells. This cytotoxicity was shown to be mediated by the T cell population of the spleen and was independent of the presence of macrophages or B cells. The time when the level of the lymphocyte-mediated cytotoxicity (LMC) to SFV-infected cells was maximal coincides with the time when immunity to SFV is maximal in vivo, as reported previously, and when adoptive immunity to SFV can be transferred. After one i.p. injection of Sindbis virus, the level of homologous LMC was higher than the level of heterologous LMC. However, following a second injection of Sindbis virus as immunogen, at a time when the mice are cross-protected to SFV, the heterologous LMC was considerably higher than homologous LMC. We propose that there is suppression of the effector T cells specific for Sindbis-infected cells after the second immunizing injection, probably by homologous antibody. In contrast, there appears to be an anamnestic cell-mediated response to SFV.
Animals↗