Accumulation of unsaturated lipids in monocytes during early phase pyrogen tolerance

Szewczenko-Pawlikowski, Malgorzata; Kozak, Wiesław

doi:10.1016/s1388-1981(00)00016-0

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…What are the known biochemical actions of LPS or zymosan activate the phospholipases A 2 , C, and D (PLA 2 , PLC, PLD) and intracellular protein kinases (e.g., PKC) (14-17); monocyte membranes are rich in phospholipases and in releasable arachidonic acid, the precursor substance for prostaglandin or leukotriene synthesis; monocyte activation correlates with changes in the composition of membrane phospholipids (18). Via PLA 2 activation, LPS induce accumulation of unsaturated lipids in monocytes, resulting in an increase in monocyte membrane fluidity (19). Thus, LPS can activate the arachidonic acid cascade (20,21).…”

Section: Discussionmentioning

confidence: 99%

Thrombin Generation by Exposure of Blood to Endotoxin: A Simple Model to Study Disseminated Intravascular Coagulation

Stief

2006

Clin Appl Thromb Hemost

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Pathologic disseminated intravascular coagulation (PDIC) is a serious complication in sepsis. In an in-vitro system consisting of incubation of fresh citrated blood with lipopolysaccharides (LPS) or glucans and subsequent plasma recalcification plasmatic thrombin was quantified. Five hundred microliters of freshly drawn citrated blood of healthy donors were incubated with up to 800 ng/mL LPS ( Escherichia coli) or up to 80 μg/mL Zymosan A (ZyA; Candida albicans) for 30 minutes at room temperature (RT). The samples were centrifuged, and 30 μL plasma were recalcified with 1 volume or less of CaCl2 (25 μmoles Ca2+/mL plasma). After 0 to 12 minutes (37°C), 20 μL 2.5 M arginine, pH 8.6, were added. Thirty microliters 0.9 m M HD-CHG-Ala-Arg-pNA in 2.3 M arginine were added, and the absorbance increase at 405 nm was determined. Fifty microliters plasma were also incubated with 5 μL 250 m M CaCl2 for 5, 10, or 15 minutes (37°C). Fifty microliters 2.5 M arginine stops coagulation, and 50 μL 0.77 m M HD-CHG-Ala-Arg-pNA in 2.3 M arginine starts the thrombin detection. The standard was 1 IU/mL thrombin in 7% human albumin instead of plasma. Arginine was also added in the endotoxin exposure time (EET) or in the plasma coagulation reaction time (CRT). Tissue factor (TF)-antigen and soluble CD14 were determined. LPS at blood concentrations greater than 10 ng/mL or ZyA at greater than 1 μg/mL severalfold enhance thrombin generation, when the respective plasmas are recalcified. After 30 minutes EET at RT, the thrombin activity at 12 minutes CRT generated by the addition of 200 ng/mL LPS or 20 μg/mL ZyA is approximately 200 mIU/mL compared to approximately 20 mIU/mL without addition of endotoxin, or compared to about 7 mIU/mL thrombin at 0 minutes CRT. Arginine added to blood or to plasma inhibits thrombin generation; the inhibitory concentration 50% (IC 50) is approximately 15 m M plasma concentration. Endotoxin incubation of blood increases neither TF nor sCD14. This assay allows the study of the hemostasis alteration in PDIC, particularly in PDIC by sepsis. The thrombin generated by blood plus endotoxin incubation and plasma recalcification suggests that the contact phase of coagulation; e.g., triggered by cell components of (phospholipase-) lysed cells such as monocyte or endothelium DNA or phospholipid-vesicles (microparticles), is of primary pathologic importance in sepsis-PDIC. Arginine at plasma concentrations of 10 to 50 m M might be a new therapeutic for sepsis-PDIC.

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Section: Discussionmentioning

confidence: 99%

Thrombin Generation by Exposure of Blood to Endotoxin: A Simple Model to Study Disseminated Intravascular Coagulation

Stief

2006

Clin Appl Thromb Hemost

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“…62 Via PLA 2 activation, LPS induce accumulation of unsaturated lipids in monocytes, resulting in an increase in monocyte membrane fluidity. 63 Thus, LPS can activate the arachidonic acid cascade. 64,65 Furthermore, LPS induce expression of PLA 2 in macrophages 66 and seem to activate oxygen radical production in monocytes.…”

Section: Susceptibility Of Cells Of the Blood Streammentioning

confidence: 99%

Coagulation Activation by Lipopolysaccharides

Stief

2007

Clin Appl Thromb Hemost

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Lipopolysaccharides at approximate plasma reactivities >3 ng/mL or beta-glucans at >0.5-1 Amicrog/mL are toxic for human blood; lipopolysaccharide interacts with membrane components of susceptible cells (eg, monocytes) activating phospholipase A(2) that destroys the cell membrane. Cell fragments (microparticles or DNA) possess polynegative niches that activate intrinsic hemostasis. Pathologic disseminated intravascular coagulation arises. Blood vessels are obstructed by disseminated thrombi, and vital organ areas become ischemic. Multiorgan failure threatens life of the patient. Diagnosis and therapy of pathologic disseminated intravascular coagulation is of extreme clinical importance. For early diagnosis of pathologic disseminated intravascular coagulation, specific activation markers of coagulation (eg, plasmatic amidolytic thrombin activity) or the plasmatic lipopolysaccharide or glucan reactivity can be measured. A new treatment target might be kallikrein or factor XIIa; 10 to 20 mM arginine is the approximate 50% inhibitory concentration against the contact phase of coagulation. The complex interaction between cell fragments and hemostasis causes pathologic disseminated intravascular coagulation in sepsis.

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Furse

Rossetti

Seiler

et al. 2002

Journal of Clinical Immunology

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Administration of gammalinolenic acid (GLA), an unsaturated fatty acid, reduces joint inflammation in patients with rheumatoid arthritis. Addition of GLA in vitro suppresses release of interleukin-1beta (IL-1beta) from human monocytes stimulated with lipopolysaccharide (LPS). LPS-induced IL-1beta release is followed by IL-1-induced IL-1beta release, an amplification process termed "autoinduction." We show here, using IL-1alpha stimulation to simulate autoinduction, that administration of GLA to healthy volunteers and to patients with inflammatory arthritis reduces LPS-induced IL-1beta secretion mainly by reducing autoinduction of IL-1beta. GLA reduces LPS-induced pro-IL-1beta mRNA modestly and IL-la-induced pro-IL-1beta gene expression markedly. In addition to reducing amplification of IL-1beta, GLA increases the amount of IL-1 receptor antagonist (IL-1Ra) secreted from stimulated cells, thereby facilitating an increase in the secreted IL-1Ra/IL-1beta ratio. IL-1beta is important to host defense, but the amplification mechanism may be excessive in genetically predisposed individuals. Thus, reduction of IL-1beta autoinduction may be protective in some patients with endotoxic shock and with diseases characterized by chronic inflammation.

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Accumulation of unsaturated lipids in monocytes during early phase pyrogen tolerance

Cited by 3 publications

References 51 publications

Thrombin Generation by Exposure of Blood to Endotoxin: A Simple Model to Study Disseminated Intravascular Coagulation

Thrombin Generation by Exposure of Blood to Endotoxin: A Simple Model to Study Disseminated Intravascular Coagulation

Coagulation Activation by Lipopolysaccharides

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