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Biomedical subjects

J Ferluga

Publications and source records attributed to J Ferluga.

31 records · Page 2Linked to original sources

Role of mononuclear infiltrating cells in pathogenesis of hepatitis.

Mice that have been injected with Corynebacterium parvum have mononuclear-cell infiltrates in the liver lobules. In such mice a small dose of lipopolysaccharide endotoxin produced a lethal hepatitis, with high serum-transaminase concentrations, glycogen depletion, and hypoglycaemia. It is suggested that lipopolysaccharide triggers the release from the infiltrating mononuclear cells of factors toxic for hepatocytes. Similarly certain parasitic and virus infections and graft-versus-host reactions can sensitise mice to the induction of hepatitis by exposure to small doses of lipopolysaccharide. This model may be applicable to human hepatitis.

Animals↗

The role of macrophage activation in chronic inflammation.

The macrophage is the characteristic cell type in chronic inflammatory reactions, in the rheumatoid synovium, as in other sites. When macrophages are activated, considerable synthesis of enzymes and other proteins occurs. Macrophages can be activated by (i) products of activated lymphocytes, (ii) immune complexes and (iii) the complement cleavage product C3b. Among the many consequences of macrophage activation are (i) secretion of hydrolytic enzymes, (ii) cleavage of C3 into C3a, which is cytolytic, and C3b, (iii) production of tissue thromboplastin, a powerful procoagulant, and (iv) formation of polyamine oxidase, which in the presence of appropriate substrates generates factors that lyse or limit the proliferation of tumour cells, lymphocytes and micro-organisms. The relevance of these observations to the pathogenesis of chronic inflammatory reactions is discussed.

Animals↗

Production of the complement cleavage product, C3a, by activated macrophages and its tumorolytic effects.

Mouse peritoneal macrophages were activated in serum-free culture with lipopolysaccharide, dextran sulphate or C3b. They were found to liberate into the culture medium a cytolytic factor and a factor which was pharmacologically indistinguishable from C3a. The cytolytic activity was neutralized by antiserum against C3a. These results suggest that macrophages can be activated by C3b (or agents that generate C3b) to cleave C3, which they themselves produce. In this way the activated macrophages form C3a, which appears to be a major factor in macrophage-mediated cytolysis. These findings have implications in tumour immunity and in the pathogenesis of inflammatory reactions.

Animals↗

Cell membranes in cytotoxicity.

Silica particles are cytotoxic for macrophages because they damage the membranes around secondary lysosomes in which the particles are engulfed. Hydroxyl groups of silicic acid on the surface of the particles form hydrogen bonds with phosphate ester groups of phospholipids and disrupt a variety of natural and artificial membranes. Asbestos fibers induce secretion of hydrolytic enzymes from cultured macrophages. Magnesium hydroxide groups of chrysotile asbestos interact ionically with ionized sialic acid residues of membrane glycoproteins, increase passive cation flux and produce osmotic lysis. The terminal components of complement (C5b-C9) when inserted into the bilayer structure also increase passive cation flux and produce osmotic lysis. The small complement cleavage product C3a is lytic for several cell types, especially malignant cells. The mechanism by which specifically sensitized thymus-derived (T)-lymphocytes kill tumour cells is discussed. Plasma membranes from effector lymphocytes possess considerable cytolytic potential, which is dependent on the activity of a membrane-associated proteinase.

Animals↗

Cytolytic effects of the complement cleavage product, C3a.

Purified C3a, a cleavage product of the third component of complement,was incubated with various cell types of human and mouse origin. All the tumour cell types tested were lysed by low concentrations of C3a, whereas normal human lymphocytes were relatively resistant. No lysis was produced by C3 or C3b. The possible role of C3a in immunity against tumours is discussed.

Animals↗

Cytotoxic activity of human lymphocyte plasma membranes.

Plasma membrane fractions isolated from normal human peripheral blood lymphocytes have considerable cytolytic activity towards a cultured human lymphoblast cell line and mouse mastocytoma cells. Other subcellular fractions, including lysosomes, have low cytolytic activity. It is suggested that this cytotoxic potential in lymphocyte plasma membranes is normally latent but can be activated by prolonged and intimate contact with target cell plasma membranes.

Cell Membrane↗