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G WEISSMANN

Publications and source records attributed to G WEISSMANN.

At least 19 recordsLinked to original sources

ACID PHOSPHATASE-RICH GRANULES IN HUMAN LYMPHOCYTES INDUCED BY PHYTOHEMAGGLUTININ.

Human lymphocytes, cultured in the presence of phytohemagglutinin, undergo morphologic transformation and subsequent mitosis. Before mitosis (48 to 72 hours), a sharp increase in acid phosphatase activity occurs in cells stimulated with phytohemagglutinin. Histochemical examination of these cells demonstrates that innumerable granules containing acid phosphatase develop in the cytoplasm before mitosis. It is possible that enzymes present in granules which stain for acid phosphatase activity (lysosome-like) may play a role in phytohemagglutinin-stimulated cell division.

Acid Phosphatase↗

STUDIES ON LYSOSOMES. IV. SOLUBILIZATION OF ENZYMES DURING MITOCHONDRIAL SWELLING AND DISRUPTION OF LYSOSOMES BY STREPTOLYSIN S AND OTHER HEMOLYTIC AGENTS.

Streptolysins S and O from hemolytic streptococci were found to induce mitochondrial swelling and the release of malic dehydrogenase from mitochondria; no other streptococcal products were as active. Mg(++), cyanide, dinitrophenol, bovine serum albumin, and antimycin all inhibited streptolysin-induced mitochondrial swelling; only the latter two agents prevented release of malic dehydrogenase from the particles. The streptolysins also solubilized beta-glucuronidase from the less numerous lysosomes of mitochondrial fractions. Vitamin A induced swelling of mitochondria with release of malic dehydrogenase and, at higher concentrations, release of beta-glucuronidase. In these effects, streptolysin S and vitamin A resembled cysteine and ascorbate, which induced swelling and lysis of mitochondria together with solubilization of enzymes. In contrast, mitochondrial swelling induced by such agents as phosphate, thyroxine, or substrates was not accompanied by release of enzymes. The release of enzymes from particles is suggested as a criterion for distinguishing "lytic" agents from those which induce mitochondrial swelling dependent upon electron transport. It was possible to dissociate effects on mitochondria and lysosomes in these experiments; less streptolysin was necessary to damage lysosomes than mitochondria; the converse was found with vitamin A. Injury to mitochondria resulted from the direct action of these agents, since the lysosomal enzymes released as a consequence of their action were not capable of inducing mitochondrial swelling or release of enzymes under the conditions studied.

Animals↗

STUDIES ON LYSOSOMES. V. THE EFFECTS OF STREPTOLYSINS AND OTHER HEMOLYTIC AGENTS ON ISOLATED LEUCOCYTE GRANULES.

Granules from rabbit peritoneal leucocytes were prepared in 0.3 M sucrose as an optically homogeneous suspension with the aid of heparin. Lysis of the granules in vitro was followed by measurement of decreases in the apparent absorbance of the suspensions at 520 mmicro and was accompanied by solubilization of beta-glucuronidase from the particles. Streptolysins O and S from hemolytic streptococci lysed the granules at 20 degrees C; the initial rate of lysis by streptolysin O was greater than that by streptolysin S. Cysteine activated, and specific antibody inhibited, streptolysin O; antimycin and bovine serum albumin inhibited streptolysin S. The granules were not lysed by any other streptococcal exotoxins. Lysis was irreversible and depended neither upon oxidative phosphorylation, nor upon intact respiration. The granules were also lysed by lysolecithin, at concentrations from 2 x 10(-6)M to 1 x 10(-4)M; bovine serum albumin and antimycin also inhibited this lytic agent. Such other hemolytic agents and procedures as vitamin A, non-ionic detergents, and ultraviolet irradiation also disrupted leucocyte granules. In susceptibility to lysis and other properties, the granules of white cells resembled erythrocytes. Leucocyte granules differed from mitochondria in that they did not appear to take up or extrude water reversibly; they were unaffected by thyroxine, phosphate, or metabolic substrate. The studies are compatible with the hypotheses that white cell granules are similar to lysosomes isolated from other tissues, and that they share common surface properties with erythrocytes.

Animals↗

LYSOSOMES.

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Cell Differentiation↗

STUDIES ON LYSOSOMES. III. THE EFFECTS OF STREPTOLYSINS O AND S ON THE RELEASE OF ACID HYDROLASES FROM A GRANULAR FRACTION OF RABBIT LIVER.

Streptolysins O and S from hemolytic streptococci have been added to granular fractions of tissue homogenates in 0.25 M sucrose prepared from rabbit liver, heart, spleen and lymph nodes. At concentrations ranging from 0.65 microg/ml to 2.0 mg/ml of streptolysin S, and from 10 microg/ml to 1.0 mg/ml of streptolysin O, two lysosomal enzymes (beta glucuronidase and acid phosphatase) and, to a lesser degree, one mitochondrial enzyme (malic dehydrogenase) were released into the supernatants of the reaction mixture. Although the hemolytic action of each lysin paralleled the effect on lysosomes, at equivalent levels of hemolytic activity, SLS was approximately 10 times more active on lysosomes than SLO. SLO was inhibited by cholesterol, cortisol, and specific antibody in vitro; pretreatment of animals with cortisone decreased the susceptibility of their isolated lysosomes to SLO. These agents failed to prevent SLS action on lysosomes. SLO had a pH optimum of 6.5 against lysosomes while SLS was maximally active at 7.5. No other streptococcal extracellular products were as active on lysosomes as the streptolysins, although activated streptococcal proteinase precursor released some hydrolases from the granules. Similarities between the actions of SLO and SLS on red cells and lysosomes suggested that the membranes bounding lysosomes and erythrocytes have common properties.

Acid Phosphatase↗

MOTION PICTURE STUDY OF THE TOXIC ACTION OF STREPTOLYSINS ON LEUCOCYTES.

The initial morphologic alteration in rabbit polymorphonuclear leucocytes exposed to streptolysin is rapid and extensive lysis of cytoplasmic granules. The granules appear to rupture directly into the cell sap. Within a few minutes following degranulation, the leucocyte rounds up, filamentous processes appear on the cell membrane, the cytoplasm liquefies, and finally the nuclear lobes swell and fuse. Streptolysin O causes these changes in intact leucocytes when added in concentrations only slightly higher than those required for release of hydrolases from isolated liver lysosomes, and furthermore exerts its action on granulocytes promptly. On the other hand streptolysin S acts on white cells only after a 15 to 30 minute delay, and the levels necessary to disrupt granules in leucocytes are considerably higher than those which act on lysosome suspensions. Exposure of rabbit alveolar macrophages to streptolysin O also results in lysis of granules, soon followed by alterations in the cytoplasm and membrane. The observations are in accord with the hypothesis that streptolysins penetrate the leucocyte membrane and bring about lysis of granules. Autolytic enzymes released from the granules might then be responsible for the subsequent damage seen in various other cell structures.

Animals↗