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Biomedical subjects

B Dewald

Publications and source records attributed to B Dewald.

At least 91 records · Page 5Linked to original sources
PubMed1982

Phagocytosis-stimulated macrophages. Production of prostaglandins and SRS-A, and prostaglandin effects on macrophage activation.

Quiescent mouse peritoneal macrophages which phagocytose, and which respond to phagocytosis with a sudden elevation in hexose monophosphate shunt activity, immediately release into the medium oxygen metabolites, arachidonic acid oxygenation products, and lysosomal hydrolases. Such cells subsequently differentiate and acquire the properties of inflammatory macrophages. The latter process appears to be under the control of prostaglandin E2 and possibly other cyclooxygenase products which are formed as a consequence of phagocytosis and seem to act as feed-back inhibitors.

Animals↗
PubMed1982

Release of gelatinase from a novel secretory compartment of human neutrophils.

Gelatinase is a metallo-proteinase that acts specifically on denatured collagen. In human neutrophils, this enzyme is localized in small, morphologically still unidentified storage organelles that are resolved from the specific and the azurophil granules upon subcellular fractionation by differential sedimentation. When neutrophils isolated from freshly drawn blood are exposed to soluble stimuli such as N-formyl-methionyl-leucyl-phenylalanine, zymosan-activated serum, phorbol myristate acetate, or the calcium ionophore A 23187, or are induced to phagocytose opsonized zymosan, they rapidly release gelatinase in large amounts (30-70% of the cellular content in 10 min). When neutrophils from donor blood, which had been stored for 24 h at 4 degrees C are used, extensive release even occurs without added stimuli by simply warming to 37 degrees C. Gelatinase release appears to occur by secretion because it is not dependent on phagocytosis. It is paralelled by the release of specific granule contents (vitamin B(12)-binding protein), but is more rapid and much more extensive. It is, however, dissociated from the discharge of azurophil granules (as assessed by beta-glucuronidase). In addition, it was found that gelatinase release does not depend on the activation of the respiratory burst, although the two responses are often observed in parallel. Release is not due to cell damage as the cytoplasmic enzyme lactate dehydrogenase is fully retained. The distinct subcellular distribution and kinetics of release of gelatinase reported in this paper uncover a novel, truly secretory compartment of human neutrophils, which is highly responsive to stimulation. Gelatinase and possibly other enzymes stored in this secretory organelle may be involved in the early events of neutrophil mobilization, the response to chemotactic signals and diapedesis.

Calcimycin↗
PubMed1981

Effects of cyclooxygenase inhibitors and prostaglandin E2 on macrophage activation in vitro.

The effect of the cyclooxygenase inhibitors, indomethacin and diclofenac, and of PGE2 on either resting or stimulated macrophages was investigated. Peritoneal macrophages were obtained from untreated mice and cultured for 10 days. Macrophage activation was induced by zymosan phagocytosis and was monitored by testing for plasminogen activator secretion and the cellular levels of lactate dehydrogenase, beta-glucuronidase and alkaline phosphodiesterase I. It was found that cyclooxygenase inhibitors activate resting macrophages and enhance the degree of activation obtained after zymosan phagocytosis. Addition of exogenous PGE2, on the other hand, had the opposite effect, it suppressed activation induced either by cyclooxygenase inhibitors, phagocytosis or a combination of both. Cyclooxygenase inhibitors and PGE2 did not affect the hexose monophosphate shunt activity of resting macrophages and had only a minor effect on the respiratory burst occurring during zymosan phagocytosis. It appears, therefore, that the observed changes in the state of activation of the macrophages are not related to hexose monophosphate shunt activity. The described effects suggest that PGE2 and possibly other cyclooxygenase products may function as inhibitory feed-back regulators of macrophage activation.

Animals↗
PubMed1981

2,3-Dihydrobenzofuran-2-ones: a new class of highly potent antiinflammatory agents.

A series of 2,3-dihydrobenzofuran-2-one analogues of the mold metabolite wortmannin, which is a powerful antiinflammatory compound, was synthesized. Most of these compounds were tested for their ability to inhibit the carrageenin paw edema and the adjuvant-induced arthritis of the rat and for their ability to inhibit prostaglandin synthesis in vitro. Indomethacin and diclofenac were used as references. The results show that compounds bearing an alkyl or aryl group in position 6 and an additional substituent, preferably chlorine, in position 5 are very powerful antiinflammatory agents and inhibitors of prostaglandin synthesis. The most active among these compounds, 5-chloro-6-cyclohexyl-2,3-dihydrobenzofuran-2-one, was significantly more potent than diclofenac in all testing models, more powerful than indomethacin in inhibiting acute inflammation and prostaglandin synthesis, and somewhat less potent than the latter compound in the adjuvant arthritis model.

Animals↗
PubMed1980

Phagocytosis stimulates the release of a slow reacting substance in cultured macrophages.

1 A slow-reacting substance (SRS) was released from non-elicited mouse peritoneal macrophages during phagocytosis of zymosan particles, whereas no detectable SRS was produced by resting cells. 2 The macrophage SRS induced a delayed and slow contraction of the guinea-pig ileum but not of the chick rectum. 3 The myotonic activity was antagonized by low concentrations of FPL 55712 (sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1 -benzopyran-2 carboxylate) but was not affected by mepyramine or hyoscine, and was not associated with tachyphylaxis. 4 SRS release was increased by indomethacin and was abolished by the lipoxygenase and cyclooxygenase inhibitor, BW755C (3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline). 5 Addition of exogenous arachidonic acid or cysteine enhanced SRS production.

Animals↗
PubMed1979

Cellular mechanisms of proteinase release from inflammatory cells and the degradation of extracellular proteins.

Neutrophils and macrophages produce, store and release large amounts of various acid and neutral proteinases. The two main proteinases of neutrophils are elastase and cathepsin G. They are localized in the azurophil granules, together with proteinase 3 and the acid cathepsins B and D. In addition neutrophils contain collagenase in the specific granules, acid proteinases in the C-particles and plasminogen activator in organelles with the characteristics of secretory vesicles. The granule-bound proteinases are released during phagocytosis while plasminogen activator is apparently secreted. In macrophages, the acid hydrolases are bound to lysosomes while the neutral proteinases are confined to secretory vesicles. The main mechanism of enzyme release in macrophages is secretion. Lysosomal hydrolases are also released by phagocytosis. Enzyme secretion is a characteristic property of activated or inflammatory macrophages. Macrophages become activated after phagocytosis of certain particles and the metabolic burst appears to be an initial event in the activation process. The action of neutrophils and of purified elastase or plasmin on cartilage was tested. These experiments indicate that neutrophil-mediated degradation of cartilage proteoglycans is largely dependent on elastase.

Animals↗
PubMed1979

Subcellular localization of the superoxide-forming enzyme in human neutrophils.

The subcellular distribution of the superoxide (O2-)-forming enzyme in human neutrophils was investigated. Cells were activated by phorbolmyristate acetate or by opsonized zymosan, and were then fractionated by zonal-rate sedimentation at two different speeds. At high speed, the specific granules were resolved from the azurophils and the membrane fraction, while at low speed, the azurophil granules could be separated from fast-sedimenting particle aggregates. Under both conditions, the major portion of the O-2--forming activity (60--70% of the total) was found to be associated with the membrane fraction which was characterized by the presence of alkaline phosphatase, alkaline phosphodiesterase I, and acid aryl phosphatase. No significant O-2--forming activity was found in either specific or azurophil granules. Some activity was present in the fastest sedimenting fractions which, as shown by electron microscopy, were heterogeneous and contained aggregated material which included membrane fragments. These fractionation results provide strong additional support for the current view that the activable O-2--forming system is localized in the plasma membrane of human neutrophils.

Cell Fractionation↗
PubMed1978

The polymorphonuclear leukocyte.

Polymorphonuclear leukocytes (PMNs) are one of the main sources of enzymes responsible for tissue damage in inflammatory processes. These enzymes are stored in two types of cytoplasmic granules. Azurophil granules contain lysosomal hydrolases, neutral serine proteinases, and bactericidal elements (myeloperoxidase and lysozyme). Specific granules contain collagenase, lysozyme and lactoferrin but lack lysosomal hydrolases. PMNs store all four classes of tissue proteinases, carboxyl, thiol and serine proteinases in the azurophil granules, and metallo proteinases in the specific granules. Three serine proteinases have been identified, elastase, cathepsin G and a third enzyme, which together account for a large proportion of the protein of the azurophil granules. In the course of phagocytic events, all these enzymes are released extracellularly. The neutral proteinases degrade proteoglycans and collagen. In vitro, they stimulate B-lymphocytes, which suggests that they may have immuno-potentiating activity when they are released at sites of chronic inflammation.

Animals↗
PubMed1978

A volume adapter for use in a B-XIV zonal rotor.

A simple adapter for reducing the chamber volume of B-XIV-type rotors is described. The adapter consists of a disk-like body, which occupies the lower part of the rotor chamber, and an aluminum sleeve with four septa. The modified rotor has a volume of 272 ml and has proved very suitable for rate-sedimentation analysis of small amounts of biological material. The modified rotor is operated as is a standard B-XIV rotor.

Animals↗
PubMed1976

In vitro stimulation of lymphocytes by neutral proteinases from human polymorphonuclear leukocyte granules.

Two neutral proteinases, polymorphonuclear leukocyte (PMN) elastase and cathepsin G, were purified from azurophil granules of human PMN. Both enzymes were found to stimulate both human and mouse lymphocytes in vitro. Experiments with mouse cells showed that the PMN proteinases are B-cell stimulants. Stimulation appears to depend on direct proteolytic action on the lymphocyte surface and not to require the mediation of serum factors of the help of T-cells.

Animals↗
PubMed1975

Subcellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes.

The subcellular localization of elastase and of neutral proteases hydrolyzing histone and casein was determined in human and rabbit polymorphonuclear leukocytes using fractionation by isopycnic centrifugation. Granule-rich fractions obtained by this technique were extracted and analyzed by acrylamide gel electrophoresis, and proteolytic activity on the gels was demonstrated by staining with either N-acetyl-D,L-alanine alpha-naphthyl ester or naphthol AS-D acetate as substrate. In both species, all neutral proteases assayed were found to be localized exclusively in the azurophil granules. Specific activities were about 10-30 times higher in human than in rabbit preparations. In extracts of human azurophil granules up to 10 proteins exhibiting esterolytic activity could be demonstrated after electrophoretic separation. Three major and two or three minor components of these esterases were shown to possess elastase activity. Similar zymograms prepared with extracts from rabbit azurophil granules revealed only one major elastase band. The electrophoretic analysis further showed that the most strongly cationic proteins of both human and rabbit PMNs were also confined to the azurophil granules.

Alkaline Phosphatase↗