Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human myelomonocytic cell line RC2a expressed procoagulant activity following stimulation with human lymphokine (LK) prepared by stimulating peripheral blood mononuclear cells with either mitogens (Concanavalin A, phytohaemagglutinin or antigen (tuberculin). Induction was rapid, with optimal activity observed between 6 and 8 h, was decreased in cultures containing serum and was not inhibited by actinomycin D or cycloheximide. The LK activity was not inhibited by an anti-interferon gamma (IFN gamma) antibody. IFN gamma and phorbol myristate acetate (PMA) had no activity but acted in synergy to induce procoagulant expression; interferon alpha plus PMA were without effect. In contrast to the LK-induced response, procoagulant induced by IFN gamma/PMA was not detected for up to 8 h and steadily rose over 24-48 h culture and was dependent on new protein and RNA synthesis. Bacterial lipopolysaccharide, a potent inducer of thromboplastin on normal human monocytes, failed, either alone or in combination with LK, IFN gamma, PMA or IFN gamma plus PMA, to activate procoagulant expression on RC2a cells. Both LK and IFN gamma/PMA-induced procoagulant had properties of thromboplastin expressed both intracellularly and on intact, viable cells. This study shows that RC2a cells are responsive to factors produced as the result of an activated cell-mediated immune response which may therefore contribute to the coagulopathies common to this form of malignancy.
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PMID:Procoagulant induction by human lymphokine and interferon gamma/PMA on a myelomonocytic cell line, RC2a. 314 14

Induction of monocyte/macrophage procoagulants may occur as the result of activation of the cell-mediated immune (CMI) response. Macrophage procoagulant inducing factor (MPIF), a soluble product of stimulated TDTH lymphocytes, may act together with two monokines, interleukin 1 and tumour necrosis factor alpha, which induce thromboplastin on endothelial cells, to initiate the fibrin deposition which is a common feature of many diseases in which CMI plays a role. Murine MPIF is chemically distinct from a number of other well characterized lymphokines in that the two major activities, MPIF alpha and MPIF beta are heparin-binding proteins with high isoelectric points. Fractions highly enriched for MPIF induced interstitial fibrin deposition when injected intradermally. In addition, intense infiltration of polymorphonuclear leucocytes (PWN) and mononuclear cells was seen 4-24 h following intradermal injection. In vitro experiments have confirmed that this lymphokine is a potent chemotactic agent for these cells. These results suggest that MPIF plays a central role in the expression of histopathological features of delayed-type hypersensitivity reactions. Monocyte and macrophage procoagulants induced by MPIF would contribute significantly to the activation of coagulation which not only results in fibrin deposition but also in the production of activated serine proteases and fibrinopeptides which may potentiate an inflammatory response.
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PMID:Coagulation and the expression of cell-mediated immunity. 330 39

Rabbit alveolar macrophages can directly stimulate either coagulation or fibrinolysis by producing tissue thromboplastin and plasminogen activator activities, respectively. However, it is not known whether these 2 opposed physiologic activities are expressed by the same or different cells within a population of alveolar macrophages. This study was undertaken to determine the distribution of procoagulant and plasminogen activator activities among density-defined populations of rabbit alveolar macrophages. Normal rabbit alveolar macrophages were separated into 4 density fractions on continuous gradients of Percoll, and the distribution of procoagulant and plasminogen activator activities among these fractions was determined. The procoagulant activity of the least dense cells (Fraction 1) was as much as 6 times greater than the activity displayed by denser cells (Fractions 2 to 4). By contrast, both cell-associated and secreted plasminogen activator activities were equally and uniformly distributed among all density fractions. These distributions of activities among density fractions persisted after the cells were incubated in culture medium for 24 h. After culture in vitro with lymphokine, procoagulant activity increased in the denser cells so that the activity became equal among all density fractions. We conclude that procoagulant activity distributes differently from plasminogen activator activity among fractions of normal rabbit alveolar macrophages separated according to cell density. By using density gradient fractionation, alveolar macrophages with predominantly procoagulant or plasminogen activator activities can be enriched from the lavage cell population; the dissimilar distribution of these 2 activities within the alveolar macrophage cell population does not reflect the presence of cells with fixed differences in their functional capacities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The distribution of procoagulant and plasminogen activator activities among density fractions of normal rabbit alveolar macrophages. 395 54

Monkey (Macaca fuscata) mononuclear leukocytes were stimulated to produce thromboplastin (tissue factor) upon exposure to lipopolysaccharide, LPS. The stimulation was dose-related in the concentration range of 10(-5) to 10(-1) micrograms/ml of LPS. Lipid A portion of the LPS molecule was essential to induce the leukocyte ability for tissue factor generation. Thus, a lipid-lipid interaction between LPS and the cells is a plausible trigger for eliciting the ability. Approximately 50% of the tissue factor thus produced appeared to be located on the cell surface, at which the coagulation cascade is probably initiated via the activation of factor VII. Among monkey mononuclear cell populations, monocytes were responsible for LPS-induced tissue factor production. Lymphocytes amplified the basal ability of monocytes to produce the factor by two-fold at physiological lymphocyte-monocyte ratios of 8:1 to 10:1. This indicates a complementary effect of lymphocytes upon the LPS-mediated monocyte ability. The medium supernatant from LPS-stimulated lymphocytes affected the monocyte competence while the stimulated lymphocytes did not. This result suggests that a soluble product of lymphocytes, i.e., lymphokine-like mediator, but not the cellular entity, participates in LPS-induced tissue factor production of monocytes.
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PMID:Monocyte thromboplastin (tissue factor): complementary effect of lymphocytes upon its generation by endotoxin-stimulated monkey (Macaca fuscata) cells. 403 Jul 40

Immune reactions are often associated with fibrin deposition. The mechanisms that lead to this fibrin formation have not yet been clarified. In this study, we show that mononuclear leukocytes (MNL) from donors with a high proliferative response to protein derivative of tuberculin (PPD) have on average 2.5 to 15-fold more thromboplastin (TP) activity, both exposed and intracellularly, compared with MNL from low responder after 4, 7 and 11 days of culture in the presence of PPD. This difference was not observed between the two groups of donors when PPD was omitted from the culture medium. Further evidence for a specific enhancement of the leukocyte TP activity can be derived from the about 4-fold increase in TP activity of the bilateral mixed leukocyte culture relative to the individually cultured controls after 7 days of incubation. TP activity was associated selectively with the monocytes in a PPD-stimulated culture of MNL. The PPD-specific enhancing effect on the leukocyte TP activity could be transferred by soluble factor(s) from stimulated lymphocytes to purified monocytes, which suggests that the effect is, at least partially, mediated by lymphokine(s).
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PMID:Enhancement of monocyte thromboplastin activity by antigenically stimulated lymphocytes: a link between immune reactivity and blood coagulation. 645 21

Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss. In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth. Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32% +/- 4.2 resorption rate was observed in the anti-cardiolipin-immunized group, which was reduced to 4% +/- 0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS.
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PMID:Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3. 847 80