The Endotoxin‐induced Coagulant Activity of Human Monocytes

Rivers, R. P. A.; Hathaway, W. E.; Weston, William L.

doi:10.1111/j.1365-2141.1975.tb00547.x

Cited by 392 publications

(167 citation statements)

References 8 publications

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“…Endotoxin can induce fibrin accumulation in vivo through the Shwartzman reaction (14), presumably by activating monocytes to express tissue factor (15). For this reason it is recognized as the component primarily responsible for blood coagulation associated with bacterial infections.…”

Section: S534 -S536) Our Results Indicate That Bacterial Proteimentioning

confidence: 99%

Activation of Human Prothrombin by Arginine-specific Cysteine Proteinases (Gingipains R) from Porphyromonas gingivalis *

Imamura

Bańbuła

Pereira

et al. 2001

Journal of Biological Chemistry

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The effect of 95-(HRgpA) and 50-kDa gingipain R (RgpB), arginine-specific cysteine proteinases from periodontopathogenic bacterium Porphyromonas gingivalis on human prothrombin activation was investigated. Each enzyme released thrombin from prothrombin in a dose-and time-dependent manner with the former enzyme, containing adhesion domains, being 17-fold more efficient than the single chain RgpB. A close correlation between the generation of fibrinogen clotting activity and amidolytic activity indicated that ␣-thrombin was produced by gingipains R, and this was confirmed by SDS-polyacrylamide gel electrophoresis, thrombin active site labeling, and amino-terminal sequence analysis of prothrombin digestion fragments. Significantly, the catalytic efficiency of HRgpA to generate thrombin (k cat /K m ‫؍‬ 1.2 ؋ 10 6 M ؊1 s ؊1 ) was 100-fold higher than that of RgpB (k cat /K m ‫؍‬ 1.2 ؋ 10 4 M ؊1 s ؊1 ). The superior prothrombinase activity of HRgpA over RgpB correlates with the fact that only the former enzyme was able to clot plasma, and kinetic data indicate that prothrombin activation can occur in vivo. At P. gingivalis-infected periodontitis sites HRgpA may be involved in the direct production of thrombin and, therefore, in the generation of prostaglandins and interleukin-1, both have been found to be associated with the development and progression of the disease. Furthermore, by taking into account that the P. gingivalis bacterium has been immunolocalized in carotid atherosclerotic plaques at thrombus formation sites (Chiu, B. (1999) Am. Heart J. 138, S534 -S536), our results indicate that bacterial proteinases may potentially participate in the pathogenesis of cardiovascular disease associated with periodontitis.

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Section: S534 -S536) Our Results Indicate That Bacterial Proteimentioning

confidence: 99%

Activation of Human Prothrombin by Arginine-specific Cysteine Proteinases (Gingipains R) from Porphyromonas gingivalis *

Imamura

Bańbuła

Pereira

et al. 2001

Journal of Biological Chemistry

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“…After incubation with Gram-negative endotoxin in vitro, blood monocytes synthesize and express membrane tissue factor (TF), a potent initiator of the coagulation cascades [1]. Mononuclear cells from patients with meningococcemia also show TF activity, that correlates with the prognosis of the disease [2].…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐10 inhibits endotoxin‐induced tissue factor mRNA production by human monocytes

et al. 1993

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In Gram-negative septic shock, human monocytes synthesize and express on their cytoplasmic membrane tissue factor (TF), a potent activator of the coagulation cascades. The role of TF in triggering disseminated intravascular coagulation (DIC) in these patients appears to be clear. We report the suppressive effect of interleukin-10 (IL-10) on endotoxin-induced TF activity and antigen levels, and on the expression of TF mRNA levels in human monocytes. These results emphasize the potential therapeutic value of this cytokine in septic shock, a condition still associated with a high mortality rate.

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“…During sepsis, bacterial mediators such as lipopolysaccharide (LPS) trigger the generation of microthrombi and the consumption of coagulation factors and their endogenous inhibitors, thereby leading to disseminated intravascular coagulation (DIC). 1,2 LPS stimulates endothelial cells 3 and blood monocytes 4,5 to express tissue factor (TF); TF then forms a highly procoagulant complex with activated factor VII (FVIIa), which initiates the coagulation cascade during endotoxemia. 6,7 Ongoing DIC causes changes in plasma levels of all coagulation factors: clinical studies reported decreased levels of FVIIa 8 and increased levels of soluble TF, 9 prothrombin fragment (F 1ϩ2 ), and soluble fibrin, resulting in increases of fibrin split products such as D-dimer.…”

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confidence: 99%

Heparin Blunts Endotoxin-Induced Coagulation Activation

et al. 1999

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Background-Lipopolysaccharide (LPS) is a major trigger of sepsis-induced disseminated intravascular coagulation (DIC) via the tissue factor (TF)/factor VIIa-dependent pathway of coagulation. Experimental endotoxemia has been used repeatedly to explore this complex pathophysiology, but little is known about the effects of clinically used anticoagulants in this setting. Therefore, we compared with placebo the effects of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) on LPS-induced coagulation. Methods and Results-In a randomized, double-blind, placebo-controlled trial, 30 healthy male volunteers received LPS 2 ng/kg IV followed by a bolus-primed continuous infusion of UFH, LMWH, or placebo. In the placebo group, activation of coagulation caused marked increases in plasma levels of prothrombin fragment F 1ϩ2 (PϽ0.01) and polymerized soluble fibrin, termed thrombus precursor protein (TpP; PϽ0.01); TF-positive monocytes doubled in response to LPS, whereas levels of activated factor VII slightly decreased and levels of TF pathway inhibitor remained unchanged. UFH and LMWH markedly decreased activation of coagulation caused by LPS, as F 1ϩ2 and TpP levels only slightly increased; TF expression on monocytes was also markedly reduced by UFH. TF pathway inhibitor values increased after either heparin infusion (PϽ0.01). Concomitantly, factor VIIa levels dropped by Ͼ50% at 50 minutes after initiation of either heparin infusion (PϽ0.01). Conclusions-This

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The Endotoxin‐induced Coagulant Activity of Human Monocytes

Cited by 392 publications

References 8 publications

Activation of Human Prothrombin by Arginine-specific Cysteine Proteinases (Gingipains R) from Porphyromonas gingivalis *

Activation of Human Prothrombin by Arginine-specific Cysteine Proteinases (Gingipains R) from Porphyromonas gingivalis *

Interleukin‐10 inhibits endotoxin‐induced tissue factor mRNA production by human monocytes

Heparin Blunts Endotoxin-Induced Coagulation Activation

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