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At least 19 recordsLinked to original sources
PubMed1978

Attack of sea urchin eggs by dogfish phagocytes: model of phagocyte-mediated cellular cytotoxicity.

To test whether lysosomal degranulation of phagocytes is associated with antibody-dependent cytotoxicity, eggs of Arbacia punctulata were used as targets for blood phagocytes of Mustelus canis. Eggs were coated with heat-aggregated dogfish IgM and exposed to phagocytes, and cytolysis of eggs was observed by Nomarski optics. Phagocytes adhered, degranulated, and raised fertilization membranes resembling those induced by sperm or ionophore A23187. Lysis was then observed as damage radiating from the point of phagocyte-egg contact. By 4 hr, coated eggs exposed to phagocytes released 8.9, 12.3, and 7.4% of total catalase (EC 1.11.1.6), beta-glucuronidase (EC 3.2.1.31), and superoxide dismutase (EC 1.15.1.1) into the medium. Cytotoxic enzyme release significantly exceeded that from uncoated eggs incubated with phagocytes or eggs alone (uncoated or coated). Because activated eggs release a neutral protease, it was considered possible that this enzyme might be responsible for autolysis of eggs. This possibility was excluded because (i) lysis of eggs was not inhibited by soybean trypsin inhibitor (SBTI) whereas the egg protease was sensitive to SBTI, and (ii) the major trypsin-like activity of phagocytes was not inhibited by SBTI. These experiments demonstrate that Ig-coated cells are first activated, and then killed, when exposed to degranulating phagocytes and suggest that enzymes from attacking phagocytes, and not target cells, are responsible for cell death.

Animals↗
PubMed1979

The intracellular survival and growth of gonococci in human phagocytes.

In reassessment of previous tests for intracellular survival, results have been confirmed and additional evidence obtained indicating that some gonococci can survive and multiply in human phagocytes. Use was made of the ability of penicillin to penetrate phagocytes and to kill only actively growing organisms. In microscopic counts on 33 urethral exudate smears, an average of 49% of gonococci were associated with polymorphonuclear phagocytes. The organisms were unevenly distributed amongst the phagocytes, with most cells uninfected and some containing large numbers. Many phagocytes also remained uninfected in tests in vitro with low gonococcal inocula although experiments with large inocula showed that most phagocytes could ingest gonococci. It is proposed that ingestion of one gonococcus may stimulate the phagocytes to take up more. Phagocytes were killed and disintegrated after ingesting large numbers of gonococci and similar effect in vivo may be responsible for the large clumps of organisms seen in urethral exudate. These results underline the probable importance in the pathogenesis of gonorrhoea of intracellular survival in phagocytes.

Blood Bactericidal Activity↗
PubMed1977

Leukocyte phagocytic function and dysfunction.

Although some species of bacteria are killed in vitro by humoral factors in cell-free serum, the in vivo experience with leukopenic patients illustrates the critical role played by phagocytic leukocytes in host resistance to infection. Effective ingestion and killing of micro-organisms requires the sequential and integrated function of the elements of the phagocytic system. Each step in the phagocytic process is also a potential crack in the armor of host defense, and an increasing number of clinically significant disorders of phagocytic function are being recognized and described (5). The phagocytic leukocytes are equipped with a variety of intracellular microbicidal mechanisms which provide a degree of overkill capacity and allow these cells to meet the challenges posed by the many and varied microbial transfressors. Undoubtedly, other phagocytic disorders will be discovered and other important aspects of the intraleukocyte killing mechanisms will be elucidated. For instance, little is known about the function of leukocytes within the relatively hypoxic environment of injured tissue where so many bacterial infections begin. As our understanding of phagocytic function develops, new ways may be found to augment host resistance by preservation or stimulation of the phagocytes.

Animals↗
PubMed1975

The role of superoxide anion generation in phagocytic bactericidal activity. Studies with normal and chronic granulomatous disease leukocytes.

The capacity of human phagocytes to generate superoxide anion (O2-), a free radical of oxygen, and a possible role for this radical or its derivatives in the killing of phagocytized bacteria were explored using leukocytes from normal individuals and patients with chronic granulomatous disease (CGD). Superoxide dismutase, which removes O2-, consistently inhibited phagocytosis-associated nitroblue tetrazolium (NBT) reduction indicating the involvement of O2- in this process. Similarly, superoxide dismutase inhibited the luminescence that occurs with phagocytosis, implicating O2- in this phenomenon, perhaps through its spontaneous dismutation into singlet oxygen. Subcellular fractions from homogenates of both normal and CGD leukocytes generated O2- effectively in the presence of NADH as substrate. However, O2- generation by intact cells during phagocytosis was markedly diminished in nine patients with CGD. Leukocytes from mothers determined to be carriers of X-linked recessive CGD by intermediate phagocytic reduction of NBT elaborated O2- to an intermediate extent, further demonstrating the interrelationship between NBT reduction and O2- generation in phagocytizing cells. Activity of superoxide dismutase, the enzyme responsible for protecting the cell from the damaging effects of O2-, was approximately equal in homogenates of normal and CGD granulocytes. Polyacrylamide electrophoresis separated this activity into a minor band that appeared to be the manganese-containing superoxide dismutase associated with mitochondria and a more concentrated, cyanide-sensitive, cytosol form of the enzyme with electrophoretic mobility that corresponded to that of erythrocyte cuprozinc superoxide dismutase. Superoxide dismutase inhibited the phagocytic killing of Escherichia coli, Staphylococcus aureus, and Streptococcus viridans. A similar inhibitory effect was noted with catalase which removes hydrogen peroxide. Neither enzyme inhibited the ingestion of bacteria. Peroxide and O2- are believed to interact to generate the potent oxidant, hydroxyl radical (.OH). A requirement for .OH in the phagocytic bactericidal event might explain the apparent requirement for both O2- and H2O2 for such activity. In agreement with this possibility, benzoate and mannitol, scavengers of .OH, inhibited phagocytic bactericidal activity. Generation of singlet oxygen from O2- and .OH also might explain these findings. It would seem clear from these and other studies that the granulo cyte elaborates O2- as a concomitant of the respiratory burst that occurs with phagocytosis. To what extent the energy inherent in O2- is translated into microbialdeath through O2- itself, hydrogen peroxide, .OH, singlet oxygen, or some other agent remains to be clearly defined.

Catalase↗
PubMed1979

Inhibition by glucocorticoids and choleragen of the conditional growth of poorly adherent mononuclear phagocytes of newborn hamster liver and lung (hormonal control of macrophage growth).

Conditions for in vitro growth of mononuclear phagocytes from newborn hamster liver and lung were studied. In the primary cultures of liver and lung, round cells outgrew and frequently floated off into the culture medium. They were separated from fibroblast-like cells adherent to plastic by collecting the medium. The round cells were identified as mononuclear phagocytes on the criteria of phagocytic capacity of heat-killed bacteria and IgG-coated erythrocytes, fine cell structure and cytochemistry. The phagocytes that had not been activated previously proliferated for about ten generations in F12 medium supplemented with 10% fetal calf serum depending on a growth factor produced by hamster brain, liver or lung cells. Without the factor, the cells quickly cytolysed. Mononuclear phagocytes from blood had the same characteristics of growth and cytochemistry, but had fewer IgG receptors at the cell surface than similar cells from the liver and lung. The effects of a variety of chemical compounds on the growth of the liver and lung cells were studied. Insulin stimulated their growth by 20-30%, but was not replaceable for the growth factor. Glucocorticoids, dexamethasone and hydrocortisone, inhibited the growth of the phagocytes at the physiological concentrations: 3 x 10(-9) M and 2 x 10(-8) M for 50% inhibition, respectively. Indomethacin, non-steroid anti-inflammatory reagent, at 10(-8) M to 10(-6) M gave no effect. Choleragen that increases the intracellular cyclic AMP level, inhibited the growth at a concentration as low as 5 pg/ml. These data suggest that the growth of mononuclear phagocytes is controlled not only by a growth factor produced by other cells but also by glucocorticoids.

Animals↗
PubMed1979

Inhibitors of membrane transport reduce lysosomal enzyme secretion from dogfish phagocytes and their killing of sea urchin eggs.

Blood phagocytes of the dogfish Mustelus canis attack oocytes of the sea urchin Arbacia punctulata, first provoking a surrogate fertilization response and then killing the eggs. To test the hypothesis that secretion of lysosomal contents is critical in this model of phagocyte-mediated cell injury, we studied effects of agents that modify lysosomal enzyme secretion. Inhibitors of membrane transport (>0.1 mM) inhibited postphagocytic secretion of lysosomal beta-glucuronidase from dogfish phagocytes: phloretin > ethacrynate > furosemide > 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid >> pyridoxal phosphate > ouabain. The same order of activity was found for inhibition by these agents of killing of Arbacia eggs by phagocytes. Cell activation (fertilization response) and cytotoxicity were quantitated both morphologically and by measurements of enzyme (beta-glucuronidase, catalase) release. The agents neither inhibited fertilization responses of eggs to calcium ionophore A23187 nor impaired their viability. Vital staining demonstrated that ethacrynate prevented phagocytes from degranulating upon contact with zymosan particles. The data not only suggest that agents primarily known for their capacity to inhibit membrane transport systems can inhibit lysosomal enzyme secretion from phagocytes but also support the hypothesis that secretion of lysosomal contents mediates activation and killing of target cells in phagocyte-mediated tissue injury.

Animals↗
PubMed1979

Characteristics of human mononuclear phagocytes.

In this study human mononuclear phagocytes from the bone marrow (promonocytes and monocytes), peripheral blood monocytes, and tissue macrophages from the skin and the peritoneal cavity were studied with respect to their morphological, cytochemical, and functional characteristics, cell surface receptors, and 3H-thymidine incorporation in vitro. The results show similarities between mononuclear phagocytes of the three body compartments with respect to esterase staining, the presence of peroxidase-positive granules, the presence of IgG and C receptors, and pinocytic and phagocytic activity. Promonocytes are the most immature mononuclear phagocytes identified in human bone marrow, and since about 80% of these cells incorporate 3H-thymidine, they are actively dividing cells. Monocytes, whether in bone marrow or the peripheral blood, and both skin and peritoneal macrophages label minimally with 3H-thymidine and thus are nondividing cells. Since the characteristics of mononuclear phagocytes in man and mouse do not diverge greatly, it is probable that the cell sequence based on in vitro and in vivo 3H-thymidine labeling studies in the mouse holds for man as well. The successive stages of development of the human mononuclear phagocyte cell line will then be as follows: monoblasts (not yet characterized in man) divide to form promonocytes, and these cells in turn divide and give rise to monocytes that do not divide further; they leave the bone marrow, circulate in the peripheral blood, and finally become macrophages in the various tissues.

Ascitic Fluid↗
PubMed1977

Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection.

Studies were made on the identity of human and monkey mononuclear leukocytes permissive to antibody-enhanced dengue 2 virus (D2V) infection. In cultures of peripheral blood leukocytes (PBL) inoculated immediately after separation, it was concluded that only mononuclear phagocytes support dengue infection. This is based upon observations that D2V-permissive cells were resistant to 1,200 rads, were both plastic adherent and nonadherent, were removed when passed through nylon wool columns in 10 percent fetal bovine serum or 100 percent autologous serum, and were destroyed by incubation with 100 mug/ml particulate silica. On direct immunofluorescence staining, perinuclear dengue antigen was visualized at 24 h, becoming maximal at 60 h. Antigen-containing cells had ample cytoplasm, ruffled cytoplasmic membrane, and 73 percent were actively phagocytic. As further evidence of the infection of mononuclear phagocytes, antibody-enhanced D2V replication was observed in bone marrow cultures from five of five rhesus monkeys, but not in cell cultures of spleen, thymus, or lymph nodes prepared from the same animals. It is hypothesized that dengue virus complexed with non-neutralizing antibody is internalized by immune phagocytosis in a mononuclear phagocyte with a defective virus-destroying mechanism. Dengue permissiveness may depend upon cellular immaturity since bone marrow leukocytes could be infected even when held for 4 days before infection while PBL held for this time decreased in permissiveness. In vitro antibody-dependent infection of mononuclear phagocytes should prove useful as a model for study of immunopathologic mechanisms in human dengue.

Animals↗
PubMed1976

Motion of spin-labeled fatty acids in murine macrophages. Relation to cellular phagocytic activity.

Macrophage membrane fluidity was investigated with respect to cellular phagocytic activity through the use of fatty acid spin labels. Spin-labeled fatty acid derivatives were incorporated into intact mouse peritoneal macrophages by exchange from bovine serum albumin. The electron spin resonance (ESR) spectra of the spin-labeled fatty acids in the macrophages showed a pronounced temperature dependence and a decrease in the hyperfine splittings (2 T11) of the spectra as the nitroxide radical was moved away from the polar head group of the fatty acid derivatives. Spin-labeled macrophages underwent a time- and temperature-dependent decay, which was inhibited by preincubating the cells with mercuric chloride, heating at 56 degrees C, or by fixing them with 0.25% glutaraldehyde. No correlation between the phagocytic activity of macrophages and membrane freedom of motion could be demonstrated. Treatment of macrophages with anti-macrophage serum or extended in vitro cultivation inhibited cellular phagocytic activity but exerted no effect on the motional freedom of the macrophage membrane. Enrichment of the fatty acid composition of the macrophage membrane with cis- or trans-unsaturated fatty acids had striking effects on cellular phagocytic activity, while no significant changes could be detected in the freedom of motion of incorporated fatty acid spin labels at the degree of specific enrichment achieved here. Thus no correlation between cellular phagocytic activity and lipid motion could be detected.

Animals↗
PubMed1978

Attachment of virulent Treponema pallidum to human mononuclear phagocytes.

The predominant phagocyte in established human syphilitic lesions is the mononuclear phagocyte. As these leucocytes may be important in immunity to Treponema pallidum, the initial interaction between human phagocytes and pathogenic T. pallidum (Nichols strain) was studied in vitro. Motile, virulent T. pallidum attach to the surface membrane of phagocytes but are not ingested by these cells. Heated, non-motile treponemes are not cell-associated but are observed free in the extracellular medium. Attachment is polar, at one or both terminal portions of the treponeme, and is neither serum- nor complement-dependent. Ingestion of virulent treponemes was not observed by phase-contrast or by electron microscopy in the presence of normal human or rabbit serum and complement. Techniques were chosen to preserve both the fragile surface constituents of the treponeme and the phagocytic function of mononuclear cells. Unfixed preparations were observed by phase-contrast microscopical examination during incubation to differentiate motile from non-motile organisms and fixed preparations were used for quantitation of attachment. This model should be useful for studying humoral and cell-mediated immunity in syphilis.

Cell Adhesion↗
PubMed1978

[Variations in the phagocytic potency of circulating leukocytes from rats which received a thermal injury. Effects of an immunostimulation with Corynebacterium granulosum (author's transl)].

Experiments were carried out to study in vitro the variations of phagocytic activity of circulating leukocytes from rats which received a thermal injury and were either immunostimulated or not by a single iv injection of C. granulosum. The thermal injury which was applied at about 10 percent of the body surface was of an intermediary type ; it developed towards necrosis before cicatrising on about the 30th day. Phagocytic activity was expressed as the percentage of "active" phagocytes or of those cells which phagocytosed Sta. aureus and S. typhi murium. In not immunostimulated rats, the phagocytic activity was profoundly depressed as a result of the thermal injury ; this was most marked at about 8 days after the thermal injury (close to 38% compared with 80% in control-not-burned-rats). The phagocytic potency or circulating leukocytes from burned and immunostimulated rats corresponded at about the 8th day to that of healthy rats. The reported variations are statistically significant, as assessed by the Student "t" and X2 tests. Our study showed that those rats which were burned in our experimental conditions responded favourably to the immunostimulation. It would be interesting to check whether the use of anaerobic corynebacteria in man could represent an adjunct treatment of those septic complications which are so frequent in severe burns.

Animals↗
PubMed1978

[Phagocytic activity of the reticuloendothelial system in the rat after administration of an anticholinesterasic pesticide, carbaryl (author's transl)].

The effects of 4 carbaryl doses (0.375, 0.75, 1.50 and 3 mg/100 g) on the reticuloendothelial system (RES) phagocytic activity were studied 1 h after their administration to male rats. Carbaryl reduced RES phagocytic activity. Results showed a dose-dependent drop in RES phagocytic activity. Carbaryl might act as an inhibitor of phagocytes by saturing them to greater or lesser degree, depending on the dose administered.

Animals↗
PubMed2024

Engineering an inducible leukemia-associated fusion protein enables large-scale ex vivo production of functional human phagocytes.

Ex vivo expansion of human CD34+ hematopoietic stem and progenitor cells remains a challenge due to rapid differentiation after detachment from the bone marrow niche. In this study, we assessed the capacity of an inducible fusion protein to enable sustained ex vivo proliferation of hematopoietic precursors and their capacity to differentiate into functional phagocytes. We fused the coding sequences of an FK506-Binding Protein 12 (FKBP12)-derived destabilization domain (DD) to the myeloid/lymphoid lineage leukemia/eleven nineteen leukemia (MLL-ENL) fusion gene to generate the fusion protein DD-MLL-ENL and retrovirally expressed the protein switch in human CD34+ progenitors. Using Shield1, a chemical inhibitor of DD fusion protein degradation, we established large-scale and long-term expansion of late monocytic precursors. Upon Shield1 removal, the cells lost self-renewal capacity and spontaneously differentiated, even after 2.5 y of continuous ex vivo expansion. In the absence of Shield1, stimulation with IFN-γ, LPS, and GM-CSF triggered terminal differentiation. Gene expression analysis of the obtained phagocytes revealed marked similarity with naïve monocytes. In functional assays, the novel phagocytes migrated toward CCL2, attached to VCAM-1 under shear stress, produced reactive oxygen species, and engulfed bacterial particles, cellular particles, and apoptotic cells. Finally, we demonstrated Fcγ receptor recognition and phagocytosis of opsonized lymphoma cells in an antibody-dependent manner. Overall, we have established an engineered protein that, as a single factor, is useful for large-scale ex vivo production of human phagocytes. Such adjustable proteins have the potential to be applied as molecular tools to produce functional immune cells for experimental cell-based approaches.

Humans↗
PubMed1977

The morphology of echinoid phagocytes and mouse peritoneal macrophages during phagocytosis in vitro.

The morphology of mouse peritoneal macrophages and echinoid phagocytes during phagocytosis in vitro was studied. A striking similarity in the function of the foreign surface receptor is found in the two systems. Glutaraldehyde-treated erythrocytes attached randomly over the entire surface of the cells and were internalized without circumferential attachment between the particles and the phagocyte membrane. The particles seemed to sink directly into the cytoplasm of the cells. Tannin-treated erythrocytes were phagocytosed by the echinoid cells in a similar mode. The complement-coated erythrocytes were attached only in the perinuclear area of the echinoid phagocyte's membrane, but the morphology of their internalization was similar to that mediated by the foreign surface receptor. A circumferential attachment between the particles and the phagocyte membrane did not seem necessary. This is also the case for mouse peritoneal macrophages.

Animals↗
PubMed1977

An in vitro assay for the quantitation of phagocytic cells of different anatomic origin.

The survival of peritoneal exudate macrophages after 3 to 10 days in culture was examined by measuring the numbers of phagocytes per culture. This was determined by letting the cultured cells phagocytize Latex particles. The number of Latex particle-containing cells was taken as a measure of the survival of phagocytes. It was found that one tenth of the cells judged by light microscopy as macrophage-like survived the culture period. Thus, the calculated plating factor of 9.3 was used to estimate the actual number of macrophages in suspensions of spleen, lymph node or thymus cells by culturing these cells and subsequently counting Latex particle-containing cells. In addition, the acridine orange technique was used to determine actual numbers of macrophages in freshly prepared cell suspensions of lymphoid organs. Latex studies on spleen and thymus cells gave results correlating well with data obtained by the acridine orange technique. By contrast, many more acridine orange positive cells than phagocytizing cells were found when lymph node cells were cultured.

Animals↗
PubMed1978

[Relationship between the phagocytic inhibition of the rat reticuloendothelial system and the anticholinesterasic effect of an insecticide, Carbaryl (author's transl)].

Phagocytic activity of the reticuloendothelial system (RES) and blood cholinesterase activity were determined in male rats after veinous administrations of carbaryl and 1-naphthol, a carbaryl metabolite. The various parameters were measured 1, 24, 48 and 72 hours after administration of the following four doses per 100 g body weight : 1.875, 3.75, 7.5 and 15 mumol. 1. Results showed an inhibition of the RES phagocytic activity (clearance of colloidal carbon) after carbaryl administration; although 1.875 mumol/100 g had no effect, the other doses inhibited RES activity, blockade time being a function of the dose given. The phagocytic function had returned to normal 72 hr after carbaryl administration. 2. Reductions in spleen weight and protein content were observed together with the RES blockade. 3. At all four doses, the anticholinesterase effect was already apparent one hour after carbaryl administration. 4. 1-naphthol, one of carbaryl's chief metabolites, had no effect either on the RES or on the different parameters studied. These results show a relationship between the phagocytic inhibition of the reticuloendothelial system and the anticholinesterasic effect by carbaryl. They suggest an inhibition of some esterases of macrophages interfering with the phagocytosis.

Animals↗