Hepatitis C and immune globulin.
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Drug Contamination↗
Biomedical subjects
S D Douglas
Publications and source records attributed to S D Douglas.
Lactate production by human monocytes/macrophages determined by proton MR spectroscopy.
Elevated brain lactate has been observed by in vivo proton MRS in different pathological situations. The origin of this lactate remains controversial. The possibility that it was produced by the metabolism of phagocytic cells has been proposed. To investigate this hypothesis, the authors have employed high-resolution proton MRS to monitor changes in glucose, lactate, and other metabolites in the medium used to culture human monocyte-derived macrophages in vitro. Results show that the differentiation of human monocytes/macrophages in the presence of physiological stimulating factors (M-CSF or GM-CSF) was associated with an increase in lactate production and glucose utilization. The present results are consistent with the hypothesis that lactate detected by proton MRS in vivo may be produced by the metabolism of macrophages when infiltrates of these cells are present. The possible extrapolation of the authors' finding to the in vivo situation and its relevance are discussed.
Cells, Cultured↗
Sleep deprivation and human immune function.
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Adult↗
Cystamine inhibits HIV type 1 replication in cells of monocyte/macrophage and T cell lineages.
The effects of cysteamine (2-aminoethanethiol, MEA) and its disulfide, cystamine, on the human immunodeficiency virus (HIV-1) expression in chronically infected promonocytic cells (U1), T cell line (ACH-2), and peripheral blood monocyte-derived macrophages (MDM) were investigated. U1 and ACH-2 cells constitutively express low levels of virus, which is increased by the addition of tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and other inducers. Cystamine, in noncytotoxic doses, suppressed in a concentration-dependent fashion the induction of HIV-1 expression mediated by TNF-alpha, IL-6, GM-CSF, and monokine-enriched monocyte culture supernatants in both U1 and ACH-2 cells as determined by HIV-1 reverse transcriptase (RT) activity. Similarly, HIV-1 expression was substantially reduced in the cystamine-treated primary MDM cultures compared with the untreated control cultures. The addition of cystamine into HIV-1 chronically infected MDM (12 days after infection was established) also suppressed 80-90% of RT activity in comparison to the untreated controls. HIV-1 (Bal) infected MDM cultures (without cystamine treatment) demonstrated giant syncytium formation, whereas cystamine-treated cultures lacked the giant syncytia induced by HIV-1 infection. Cystamine also inhibited LPS-induced TNF production in MDM. In contrast to cystamine, cysteamine showed no significant effects on either the monokine-induced HIV-1 expression in U1 or ACH-2 or acute and chronic HIV-1 infection in MDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Antiviral Agents↗
Immunological and virological clues for mother-to-child transmission of HIV-1 and HIV-2.
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Adult↗
Bovine parainfluenza-3 virus selectively depletes a calcium-independent, phospholipid-dependent protein kinase C and inhibits superoxide anion generation in bovine alveolar macrophages.
Bovine parainfluenza-3 (PI-3) virus inhibits oxygen-dependent bacterial killing by phagocytes, a key pulmonary defense, thus predisposing the host to intrapulmonary bacterial superinfection. PI-3 virus inhibited opsonized zymosan or PMA-activated superoxide anion (O2-) generation in bovine alveolar macrophages. The respiratory virus influenza also inhibits O2- generation by phagocytes, however, the mechanisms(s) of viral inhibition differs from PI-3. PI-3 did not trigger O2- generation before inhibition, whereas influenza triggered O2- generation before desensitization of ligand-initiated respiratory burst. PI-3 modified the twin signals of calcium and protein kinase C in alveolar macrophages. PI-3 infection increased macrophage membrane permeability to extracellular calcium, but did not inhibit calcium mobilization triggered by opsonized zymosan. These effects further distinguish bovine PI-3 from human influenza, which triggers mobilization of cell-associated calcium and inhibits calcium mobilization activated by physiologic ligands. Macrophages possessed two classes of PKC activity, a calcium/phosphatidylserine/diglyceride (Ca/PS/DG))-dependent activity and a Ca-independent, PS/DG-dependent histone IIIS phosphorylating activity. PI-3 infection selectively depleted the Ca-independent, PS/DG-dependent kinase activity but not the classical Ca/PS/DG-dependent activity. Inhibition of Ca-independent, PS/DG-dependent kinase activity and inhibition of O2- generation by PI-3 occurred at a similar viral dose and time frame, suggesting a role for this kinase in activating the respiratory burst. Inhibition of the oxygen-dependent bactericidal function of alveolar macrophages and disturbances in signal transduction may contribute to the immunosuppression and bacterial superinfection accompanying viral respiratory disease.
Animals↗
Autoimmune hemolytic anemia in chronic mucocutaneous candidiasis.
Chronic mucocutaneous candidiasis is an immunodeficiency disease characterized by T-cell dysregulation and chronic superficial candidal infections. We report on three patients with chronic mucocutaneous candidiasis who developed autoantibodies to erythrocytes. Our first patient, a 19-year-old female, developed autoimmune hemolytic anemia (AIHA) that required multiple courses of treatment, including corticosteroids, intravenous immunoglobulin, and danazol. During the last exacerbation of AIHA, intensive treatment with corticosteroids and intravenous immunoglobulin failed and yet the patient responded to plasmapheresis. Our second patient, a 21-year-old male, developed AIHA which responded to oral corticosteroid therapy. Our third patient, a 6-year-old female without evidence of hemolysis, was found to have erythrocyte autoantibodies on routine screening. These three patients had positive direct antiglobulin tests, and the first patient had both immunoglobulin G (IgG) and IgM erythrocyte autoantibodies, while the remaining two patients had only IgG autoantibody. This is the first report of the association of AIHA with chronic mucocutaneous candidiasis. We suggest that all patients with chronic mucocutaneous candidiasis be screened periodically for erythrocyte autoantibodies. Plasmapheresis, a safe ancillary procedure in the management of AIHA, may be life-saving in some cases. The occurrence of erythrocyte autoantibodies in mucocutaneous candidiasis may be related to immunoregulatory disorders in this disease.
Adolescent↗
Flow cytometric measurement of immunoglobulin E to natural latex proteins.
Immediate hypersensitivity to natural latex (NL) occurs in sensitized individuals after repeated exposure to products or devices containing NL components. Since allergic reactions to NL proteins are quite frequent and may be quite serious, diagnostic assays are needed to identify individuals at risk. A number of latex proteins have been considered the major antigens, but they have been incompletely characterized. There is no standard material available for skin testing. In vitro diagnostic tests, such as the radioallergosorbent test (RAST), are time consuming and their sensitivity and specificity remain to be proven. We have developed a rapid microsphere-based, fluorescence-activated flow cytometry assay for the measurement of NL protein-specific human immunoglobulin E and have compared it with both the enzyme-linked immunosorbent assay and radioallergosorbent test methods. By using the total purified NL protein fraction isolated from raw ammoniated NL sap as the antigen, the flow cytometry assay was both sensitive and specific for the detection of NL protein-specific human immunoglobulin E in the sera of sensitized pediatric patients.
Adolescent↗
Substance P augments tumor necrosis factor release in human monocyte-derived macrophages.
Substance P (SP) is an undecapeptide that has the amino sequence Arg-Pro-Lys-Pro-Gin-Gln-Phe-Phe-Gly-Leu-Met-NH2 and that belongs to a family of structurally related peptides known as tachykinins, the latter are widely distributed in the central nervous system. SP is involved in the biological activities of cells in the immune system, including the induction of cytokines in immune cells. We have investigated the effects of SP on constitutive and/or lipopolysaccharide (LPS)-induced expression of tumor necrosis factor (TNF) in cultured blood monocyte-derived macrophages (MDM). Cells cultured in vitro for 14 days were treated with SP at various concentrations (10(-10) to 10(-6M) in the presence of LPS before culture supernatants were harvested. TNF bioactivity in culture supernatants was measured with L929 cell line MDM from 10 of 12 donors treated with a SP alone showed increased TNF production. SP and LPS also interacted in a synergistic fashion in upregulating TNF production in MDM from responders. The stimulatory effect of SP was inhibited by two SP antagonists, spantide ([D-Arg-1-D-Trp-7-D-Trp-7-D-Trp-9-leu-11]-SP) and CP-96,345 (a nonpeptide antagonist of the SP receptor). In addition, an anti SP polyclonal antibody blocked the SP effect on TNF production in cultured MDM, further indicating the specificity of these effects. These results demonstrate that SP is an important regulator of monokine production by human monocytes/macrophages.
Antibodies, Blocking↗
Monokine-mediated increase in human immunodeficiency virus type 1 expression in chronically infected promonocyte- and T-cell-derived lines.
The ACH-2 cell clone derived from a human T-cell line and chronically infected with human immunodeficiency virus 1 (HIV-1) and the U1 cell clone derived from a human promonocyte cell line and also chronically infected with HIV-1 produce HIV-1 in a response to stimulation with monokine-enriched supernatants prepared from highly purified populations of peripheral blood-derived human monocytes. Monokine-mediated expression of HIV-1 in these cell lines resulted in augmented virus production reflected by increases in reverse transcriptase (RT) activity, production of p24 antigen, and synthesis of major viral proteins. Examination of the cells by electron microscopy revealed numerous HIV-1 virions in the cells treated with the supernatants. This stimulation of virus production by monokine-enriched supernatants resulted in approximately 100-fold increases in RT activity and p24 antigen expression in comparison with those in untreated U1 and ACH-2 cells. Absorption of monokine-enriched supernatants with rabbit anti-tumor necrosis factor alpha antibody removed most, but not all, of the induced HIV-1 RT activity and p24 antigen expression in U1 and ACH-2 cell lines, suggesting that tumor necrosis factor alpha in the monokine-enriched supernatants is a major factor in the induction of HIV-1 expression in these cells.
Adult↗
DNA-based HLA typing of nonhematopoietic tissue used to select the marrow transplant donor for successful treatment of transfusion-associated graft-versus-host disease.
Transfusion-associated graft-versus-host disease (TAGVHD) is a rare and usually fatal complication of blood transfusion which can arise when immunocompetent lymphocytes from the donor of a cellular blood product are transfused into a severely immunocompromised recipient. We describe the case of an 8-month-old male with a severe combined immunodeficiency syndrome who developed TAGVHD after receiving an unirradiated transfusion. Serologic HLA typing of the parents, the patient, and the blood donor demonstrated the foreign origin of circulating lymphocytes, confirming the diagnosis of TAGVHD. The manifestations of TAGVHD did not respond to medical immunosuppressive therapy, and bone marrow transplantation was planned to treat the underlying immunodeficiency as well as the TAGVHD. By using DNA-based class I and class II HLA typing, the child's HLA type was determined from nonhematopoietic tissues. This information proved critical in selecting the bone marrow donor. The child received immunosuppression, myeloablation, and a T-depleted, maternal bone marrow graft mismatched at one HLA class II allele. Trilineage hematopoietic engraftment occurred within 3 weeks, and the child remains clinically stable with no evidence of TAGVHD more than 2 years after the transplant. This case illustrates that TAGVHD can be successfully treated by allogeneic bone marrow transplantation and that DNA-based HLA typing can play a unique role in the diagnosis and management of TAGVHD.
Bone Marrow Transplantation↗
Effect of hematopoietic growth factors on human blood monocytes/macrophages in in vitro culture.
The production of mature monocytes/macrophages is regulated by a group of hematopoietic growth factors, or colony-stimulating factors (CSF). We investigated the in vitro effect of human hematopoietic growth factors on human blood monocyte/macrophage differentiation and proliferation in short- and long-term in vitro cultures. The addition of macrophage CSF, granulocyte-macrophage CSF, and granulocyte CSF and interleukin-6 and interleukin-3 growth factors to monocyte/macrophage cultures induced morphological changes in cultured cells, including enhancement of cell growth and the formation of multinucleated giant cells, spindle-like cells, and fibroblast-like cells. In addition, CD4 and HLA-DR antigen expression was down regulated by the addition of growth factors without a change in the expression of other surface antigens, including CD3, CD11B, CD14, CD15, NK H1, and B1. The proliferating cell nuclear antigen was not detected in growth factor-treated nonadherent monocytes/macrophages in long-term cultures. Bromodeoxyuridine was incorporated in the adherent monocytes/macrophages, and intense staining in the small rounded cells which occur above the adherent cells in these cultures was observed after a 72-h pulse, indicating that monocytes/macrophages are slowly dividing cells.
Antigens, CD↗
Placental transfer of immunoglobulin G subclasses.
The concentrations in cord blood of total immunoglobulin G (IgG) and the four subclasses of IgG were measured in 34 fetuses at a mean gestational age of 25 weeks (range, 18 to 35 weeks). The blood samples were obtained by percutaneous umbilical blood sampling, and results were compared with the respective IgG subclass concentrations of the mothers. The efficiency of transplacental transfer of the different IgG subclasses was determined. Transfer of IgG1 and IgG4 was found to be significantly more efficient than that of IgG3 and IgG2. IgG2 was the subclass least efficiently transferred from mother to fetus. These differences may partly explain the susceptibility of newborns to various pathogens, such as streptococcus group B.
Female↗
Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation.
The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep.
Adult↗
In vitro and in vivo effects of granulocyte colony-stimulating factor on neutrophils in glycogen storage disease type 1B: granulocyte colony-stimulating factor therapy corrects the neutropenia and the defects in respiratory burst activity and Ca2+ mobilization.
Children with glycogen storage disease (GSD) type 1b are susceptible to recurrent bacterial infections and have chronic neutropenia accompanied by phagocytic cell dysfunction including decreased superoxide anion (O2-) generation, calcium (Ca2+) mobilization, and chemotactic activity. Granulocyte colony-stimulating factor (G-CSF), a cytokine that corrects neutropenia in other diseases, in vitro enhances f-Met-Leu-Phe-triggered neutrophil O2- generation. Short-term pretreatment (15 min) of GSD 1b neutrophils with G-CSF increased the rate of O2- production (p < 0.01); however, this rate was still significantly below the rate of O2- production in control neutrophils. Recombinant human G-CSF (5 micrograms/kg/d) was administered s.c. to a GSD 1b patient. Before treatment, absolute neutrophil counts were < 500/mm3. Two d after G-CSF administration, the absolute neutrophil counts increased to 1333 and remained in the normal range during a 12-mo follow-up period. In vivo, G-CSF therapy increased f-Met-Leu-Phe-stimulated O2- production to 52% of control after 1 mo, and by mo 4, O2- production reached control levels. Our previous studies (J Clin Invest 56:196-202, 1990) demonstrated that decreased O2- production in neutrophils was associated with impaired Ca2+ mobilization. In vivo administration of G-CSF increased f-Met-Leu-Phe-triggered Ca2+ mobilization by neutrophils to 43% of control by mo 1 of G-CSF therapy and to 93% of control by mo 4, thus paralleling the improvements in O2- generation. In contrast, G-CSF therapy had no effect on the defective neutrophil chemotaxis. In summary, G-CSF therapy produced a rapid increase in circulating neutrophils and a gradual correction of O2- production.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
The macrophage and HIV-1.
As described above, monocytes/macrophages from such diverse areas as the CNS, lungs, peripheral blood, cord blood, and liver are susceptible to infection by HIV-1 and may serve as reservoirs for transmitting the virus throughout the body. In contrast to lymphocytes, the chronic and low-level mode of infection that HIV-1 takes on within monocytes/macrophages allows these cells to contribute to persistent viral infection. Infection of these cells by HIV-1 can alter a variety of their immunological functions such as cytokine production, chemotaxis, accessory cell function, and microbicidal activity. Furthermore, macrophages and macrophage-related microglial cells in the brain and CSF are thought to play a critical role in the pathogenesis of CNS disease. Infection with HIV-1 in monocytes/macrophages is regulated in an autocrine manner by a panel of cytokines and other soluble factors. Most HIV-1 isolates exhibit specific tropism for monocytes/macrophages, lymphocytes, or, in some cases, both cell types; this phenomenon of tropism may be linked to structural variabilities between different isolates. While in vitro studies clearly demonstrate that the replicating cycle of HIV-1 in monocytes/macrophages differs from its replicating cycle in lymphocytes, elucidation of the role of monocyte/macrophages in mediating the severe immunosuppression characteristic of AIDS is far more from complete, and further investigation into the role of monocytes/macrophages in the immunopathogenesis of HIV-1 infection is necessary to design therapeutic approaches to control viral infection and disease progression.
AIDS Dementia Complex↗
Centrifugal enhancement of human immunodeficiency virus type 1 infection and human cytomegalovirus gene expression in human primary monocyte/macrophages in vitro.
In an effort to facilitate the efficiency of human immunodeficiency virus type 1 (HIV-1) and/or human cytomegalovirus (HCMV) infection in primary monocyte/macrophages in vitro, the effect of low-speed centrifugation was studied. The infectivity of three strains (Bal, Ada-M, and IIIB) of HIV-1 tested was significantly enhanced by centrifugal inoculation at a force of 1500g for 60 min. Reverse transcriptase activity and HIV-1 p24 antigen in primary monocyte/macrophages infected by a centrifugal inoculation technique were detectable 3-7 days earlier and were more than 10-fold greater in magnitude (at an early stage of the infection) than those of control cells infected by the conventional inoculation technique. Examination of the cells by indirect immunofluorescence revealed higher expression of HIV-1 p24 protein in the monocyte/macrophages infected by the centrifugal inoculation technique. These differences were directly related to centrifugal inoculation and were evident up to 3 weeks after infection. Enhancement was not observed when centrifugation was carried out before or after HIV-1 infection. Centrifugal inoculation of HCMV also enhanced its immediate-early and early gene expression up to 30- to 50-fold, although neither late nuclear antigens and glycoproteins of HCMV nor infectious virus was detected in HCMV-infected monocyte/macrophage cultures. These results show that centrifugal inoculation is a useful technique for improving the efficiency of HCMV and HIV-1 infection in vitro.
Cells, Cultured↗
Enhancement in vitro of the low interferon-gamma production of leukocytes from human newborn infants.
Interferon-gamma (IFN-gamma), a lymphokine produced by lymphocytes with the help of monocytes, is essential for host resistance to intracellular pathogens. Leukocytes from normal term newborn infants cannot produce IFN-gamma in vitro in response to stimulation by antigen or mitogens in vitro or in vivo. We investigated the production of IFN-gamma in vitro using endotoxin from Salmonella typhimurium as a stimulus. In contrast to those from adults, mononuclear cells derived from the cord blood of newborn infants did not produce IFN-gamma in response to this endotoxin. We investigated the contribution of the functional immaturity of cord blood monocytes to this relative inability to produce IFN-gamma. Aging of the monocytes for 2 weeks in vitro or treatment of freshly isolated cord blood monocytes with conditioned medium (from cultures of mononuclear cells from healthy adults) greatly enhanced IFN-gamma production stimulated by endotoxin. Furthermore, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), or IFN-gamma was able to substitute in part for the conditioned medium from adult cells. Thus correction of the functional immaturity of monocytes derived from newborn infants can result in enhanced production of IFN-gamma in vitro.
Adult↗