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Biomedical subjects

H Northoff

Publications and source records attributed to H Northoff.

116 records · Page 7Linked to original sources

Cytotoxicity of human mononuclear cells against chicken and human red blood cells, induced by treatment of the effector cells with phospholipase C.

Human mononuclear cells from peripheral blood which were treated with phospholipase C (PLC), became cytotoxic against human or chicken red blood cells. PLC-induced cellular cytotoxicity against human red blood cells was further analyzed and compared to anti-D-mediated, antibody-dependent cellular cytotoxicity (ADCC), using the same target cells. ADCC, but not cytotoxicity of PLC-treated effector cells, was inhibited by free IgG. In addition, iodoacetate strongly enhanced PLC-induced cytotoxicity, but blocked ADCC completely. Addition of fetal calf serum or human AB serum impaired PLC-induced cytotoxicity. A similar inhibition was found by adding lecithin liposomes suggesting that the inhibitory effect of sera was also due to their phospholipid content. The data show that cytotoxicity of PLC-treated effector cells can be clearly distinguished from cellular cytotoxicity, occurring spontaneously or induced by target cell antibodies. We favor the notion that cytotoxicity of PLC-treated effector cells against human erythrocytes is due to the action of PLC, adsorbed to the effector cells.

Absorption↗

Antibody dependent cellular cytotoxicity (ADCC) against human erythrocytes, mediated by blood group alloantibodies: a model for the role of antigen density in target cell lysis.

Antibody dependent cellular cytotoxicity (ADCC) of human mononuclear cells against human erythrocytes could be obtained with anti-A and anti-D sera. The degree of lysis varied considerably depending on the antigen system and on the experimental conditions. Anti-D mediated in contrast to anti-A mediated ADCC turned out to be very sensitive to conditions which interfere with target cell lysis: for most of the anti-D sera, removal of unbound IgG was found to be crucial to detect their ability to mediate ADCC. Pretreatment of the target cells with various enzymes dramatically improved specific lysis and left spontaneous release and spontaneous cytotoxicity essentially unaffected. In the case of neuraminidase treatment it could be shown that the effect was independent from the exposure of additional binding sites. When enzyme treatment and removal of excess IgG were applied in combination, as little as 10(4) antigenic determinants proved to be sufficient to induce specific lysis.

Antibody-Dependent Cell Cytotoxicity↗

Lipopolysaccharide-induced elaboration of interleukin 1 by human monocytes: use for detection of lipopolysaccharide in serum and the influence of serum-lipopolysaccharide interactions.

An assay of interleukin 1 (IL-1) production by human monocytes was used to detect minute amounts of bacterial lipopolysaccharide (LPS) in sera or serum components designed for use in experiments or for injection into humans. Elaboration of IL-1 is a more sensitive criterion for the presence of LPS than is the rabbit pyrogenicity assay, and contamination of a given solution with LPS can be semiquantitatively determined by comparison with a standard. Interaction of (exogenously added) LPS with serum interferes with the recognition of LPS by monocytes but in a manner different from that encountered in the limulus test. Recognition of LPS by monocytes was not affected by the presence of naturally occurring antibodies to LPS. With use of IL-1 elaboration as an indicator, the presence of functionally active LPS in the sera of some patients with sepsis could be demonstrated.

Adult↗

Tumor necrosis factor: a cytokine involved in toxic effects of endotoxin.

Endotoxin-induced tumor necrosis has been shown to be mediated by a factor termed tumor necrosis factor (TNF). The biochemical nature, source, and mode of induction of TNF have been clarified. TNF is a mediator of activated macrophages that is released into the supernatant by these cells after their stimulation with endotoxin. A number of biologic functions of TNF other than its tumoricidal activity have been demonstrated. In vivo, TNF induces reactions similar to those induced by endotoxin. Hypothermia, elevated hematocrit and plasma lactate levels, and reduced plasma glucose levels have been measured in mice injected with TNF. These reactions typically occur soon after endotoxin injection and are induced with purified recombinant TNF in mice that exhibit a low response to endotoxin. No TNF-induced production of interleukin 1 (which can induce similar effects) was detected in macrophage/monocyte cultures. Therefore, TNF appears to mediate endotoxin effects directly.

Animals↗

Production of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 in the perfused rat liver.

The kinetics of the production and release of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6) were investigated in the perfused rat liver and in primary cultures of Kupffer cells after stimulation with lipopolysaccharide (LPS). A small and transient accumulation of TNF-alpha could be detected immunohistochemically and by cytotoxicity assay in the intracellular space about 1 h after addition of LPS to the cultured cells. TNF-alpha release in the perfused liver followed similar kinetics as those found in the serum of LPS-treated rats and in primary cultures of rat Kupffer cells. The cytotoxic TNF-alpha activity of the perfusate attained its maximum (11.5 +/- 2.6 U/ml) 90 min after LPS stimulation and remained nearly constant for further 150 min. 2 microM dexamethasone reduced the production of TNF-alpha by 10 g of liver during 240 min from 46 to 16 x 10(3) units. The production of IL-1 and IL-6 by 10 g of liver during the initial 240 min was 3 and 530 x 10(3) IU, respectively. The maximal concentrations of IL-1 (1.4 +/- 0.7 IU/ml) and IL-6 (157 +/- 60 IU/ml) were found 240 min after LPS addition. The production of IL-1 was totally suppressed by 2 microM dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗