Differential Effects of Reconstituted High-density Lipoprotein on Coagulation, Fibrinolysis and Platelet Activation during Human Endotoxemia

Dasja Pajkrt; Peter G Lerch; Tom van der Poll; Marcel Levi; Marlies Illi; Jan E Doran; Beat Arnet; Abraham van den Ende; Jan Wouter ten Cate; Sander J H van Deventer

doi:10.1055/s-0038-1655958

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 77(02): 303-307
DOI: 10.1055/s-0038-1655958

Original Article

Schattauer GmbH Stuttgart

Differential Effects of Reconstituted High-density Lipoprotein on Coagulation, Fibrinolysis and Platelet Activation during Human Endotoxemia

Dasja Pajkrt

¹Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

,

Peter G Lerch

²ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland

,

Tom van der Poll

¹Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

,

Marcel Levi

³Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

,

Marlies Illi

²ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland

,

Jan E Doran

²ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland

,

Beat Arnet

²ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland

,

Abraham van den Ende

³Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

,

Jan Wouter ten Cate

³Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

,

Sander J H van Deventer

¹Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

› Author Affiliations

Abstract

PDF Download

Summary

High-density lipoproteins (HDL) can bind and neutralize lipopoly- saccharides (LPS) in vitro and in vivo. HDL can also affect fibrinolytic activity and can directly influence platelet function by reducing platelet aggregation. In this study, the effects of reconstituted HDL (rHDL) on LPS-induced coagulation, fibrinolysis and platelet activation in humans were investigated. In a double-blind, randomized, placebo-controlled, cross-over study, eight healthy male volunteers were injected with LPS (4 ng/kg) on two occasions, once in conjunction with rHDL (40 mg/kg, given as a 4 h infusion starting 3.5 h prior to LPS injection), and once in conjunction with placebo. rHDL significantly reduced LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1+2) and fibrinolysis (plasma levels of tissue type plasminogen activator antigen, t-PA). No effect was observed on LPS-induced inhibition of the fibrinolytic pathway (PAI-1) or on the transient thrombocytopenia elicited by LPS. Furthermore, rHDL treatment significantly enhanced the inhibition of collagen-stimulated inhibition of platelet aggregation during endotoxemia, but had no such effect on arachido- nate-stimulated platelet aggregation. rHDL treatment per se also reduced collagen-induced platelet aggregation. These results indicate that rHDL modifies the procoagulant state associated with endotoxemia.

PDF (399 kb)

References

References
1 Gawaz M, Fateh-Moghadam S, Pilz G, Gurland HJ, Werdan K. Platelet activation and interaction with leucocytes in patients with sepsis and multiple organ failure. Eur J Clin Invest 1995; 25: 843-851
2 Levi M, ten Cate H, van der PollT, van Deventer SJH. Pathogenesis of disseminated intravascular coagulation in sepsis. JAMA 1993; 270: 975-979
3 ten Cate H, Brandjes DPM, Wolters HJ, van DeventerSJH. Disseminated intravascular coagulation: pathophysiology, diagnosis, and treatment. New Horizons 1993; 01: 312-323
4 Emancipator K, Csako G, Elin RJ. In vitro inactivation of bacterial endotoxin by human lipoproteins and apolipoproteins. Infect Immun 1992; 60: 596-601
5 Suffredini AF, Harpel PC, Parillo JE. Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects. N Engl J Med 1989; 320: 1165-1172
6 Van Deventer SJH, Büller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation fibrinolytic, and complement pathways. Blood 1990; 76: 252-256
7 Csako G, Suba EA, Elin RJ. Endotoxin-induced platelet activation in human whole blood in vitro. Thromb Haemost 1998; 59: 378-382
8 Stuart MJ. Effect of endotoxin on arachidonic acid release and thromboxane B₂ production by human platelets. Am J Hematol 1981; 11: 159-164
9 Gralnick HR, Elin R, Abrans E, Givelber H, Wolff SM. Effects of endotoxin (LPS) on blood coagulation in humans. Clin Res 1976; 24: 344A
10 Cohen P, Braunwald J, Gradner FH. Destruction of canine platelets and rabbit platelets following intravenous administration of carbon particles or endotoxin. J Clin Lab Med 1965; 66: 263-271
11 Fletcher JG, Ramwell PW. The effects of prostacyclin (PGI₂) on endotoxic shock and endotoxin-induced platelet aggregation in dogs. Circ Shock 1980; 07: 299-308
12 Spielvogel AR. An ultrastructural study of the mechanisms of platelet-endotoxin interaction. J Exp Med 1967; 126: 235-250
13 Flegel WA, Wӧlpl A, Mӓnnel DA, Northoff H. Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins. Infect Immun 1989; 57: 2237-2245
14 Baumberger C, Ulevitch RJ, Dayer JM. Modulation of endotoxin activity of lipopolysaccharide by high-density lipoprotein. Pathobiology 1991; 59: 378-383
15 Flegel WA, Baumstark MW, Weinstock C, Berg A, Northoff H. Prevention of endotoxin-induced monokine release by human low-and high-density lipoproteins and by apolipoprotein A-l. Infect Immun 1993; 61: 5140-5146
16 Levine DM, Parker TS, Donelly TM, Walsh A, Rubin AL. In vivo protection against endotoxin by plasma high density lipoprotein. Proc Natl Acad Sci USA 1993; 90: 12040-12044
17 Parker TS, Levine DM, Chuang JCC, Laxer J, Coffin CC, Rubin AL. Reconstituted high-density lipoprotein neutralizes gram-negative bacterial lippolysaccharides in human whole blood. Infect Immun 1995; 63: 253-258
18 Hubsch AP, Powell FS, Lerch PG, Doran JE. A reconstituted apolipoprotein A-l containing lipoprotein reduces tumor necrosis factor release and attenuates shock in endotoxemic rabbits. Circulatory Shock 1993; 40: 14-23
19 Cue JI, Di Piro JT, Brunner LJ, Doran JE, Blankenship ME, Mansberger AR, Hawkins ML. Reconstituted high-density lipoprotein inhibits physiologic and tumor necrosis factor a responses to lipopolysaccharide in rabbits. Arch Surg 1994; 129: 193-197
20 Feingold KR, Funk JL, Moser AH, Shigenaga JK, Rapp JH, Grunfeld C. Role of circulating lipoproteins in protection from endotoxin activity. Infect Immun 1995; 63: 2041-2046
21 Malyszko J, Urano T, Knofler R, Ihara H, Takada Y, Takada A. Relationships between serum lipids serotonin, platelet aggregation and some fibrinolysis parameters in humans. Life Science 1994; 55: 1619-1623
22 Koller E, Koller F, Doleschel W. Specific binding sites on human platelets for plasma lipoproteins. Hoppe-Seyler’s Z Physiol Chem 1982; 363: 395-405
23 Koller E, Koller F, Binder BR. Purification and identification of the lipoprotein-binding proteins from human blood platelet membrane. J Biol Chem 1989; 264: 12412-12418
24 Malle E, Sattler W. Platelets and lipoproteins: native, modified and platelet modified lipoproteins. Platelets 1994; 05: 70-83
25 Surya II, Akkerman JWN. The influence of lipoproteins on blood platelets. Am Heart J 1993; 125: 272-275
26 Pajkrt D, Doran JE, Koster F, Lerch PG, Arnet B, van der PollT, ten Cate JW, van Deventer SJH. Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. J Exp Med 1996; 180: 1601-1608
27 Lerch PG, Fortsch V, Hodler G, Bolli R. Production and characterization of a reconstituted high density lipoprotein (rHDL) for therapeutic applications. Vox Sang 1996; 71: 155-164
28 Von der MӧhlenMAM, Kimmings AN, Wedel NI, Mevissen MLCM, Jansen J, Friedmann N, Lorenz TJ, Nelson BJ, White ML, Bauer R, Hack CE, Eerenberg A, van Deventer SJH. Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans using recombinant bactericidal/permeability-increasing protein (rBPI₂₃). J Infect Dis 1995; 172: 144-151
29 Van derPoll T, Levi M, Hack CE, van Deventer SJH, ten Cate H, Haagmans B, Biemond BJH, Büller HR, ten Cate JW. Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 1994; 83: 446-451
30 Van derPoll T, Levi M, Hack CE, ten Cate H, van Deventer SJH, Eerenberg AJM, de Groot ER, Jansen J, Gallati H, Büller HR, ten Cate JW, Aarden LA. Elimination of Interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med 1994; 179: 1253-1259
31 Saku K, Ahmad M, Glas-Greenwalt P, Kashyap ML. Activation of fibrinolysis by apoliporoteins of high denity lipoproteins in man. Thromb Res 1985; 39: 01-08
32 Epand RM, Stafford A, Leon B, Lock PE, Tytler EM, Segrest JP, Anantha-ramaiah GM. HDL and Apolipoprotein A-l protect erythrocytes against the generation of procoagulant activity. Arterioscler Thromb 1994; 14: 1775-1783
33 Waysbort J, Schwartz S, Brunner D. Effect of bezafibrate on lipids lipoproteins, apolipoproteins and platelet aggregation in hypertriglyceridemic patients. Arzneim Forsch 1994; 44: 1217-1222
34 Sermet A, Aybak M, Ulak G, Guzel C, Denli O. Effect of oral pyridoxine hydrochloride supplementation on in vitro platelet sensitivity to different agents. Arzneim Forsch 1995; 45: 19-21
35 Higashihara M, Kinoshita M, Teramoto T, Kume S, Kurokawa K. The role of ApoE in inhibitory effects of apoE-rich HDL on platelet function. FEBS 1991; 282: 82-86
36 Yui Y, Aoyama T, Morishita H, Takahashi M, Takatsu Y, Kawai C. Serum prostacyclin stabilizing factor is identical to apolipoprotein A-l (apoA-1). J Clin Invest 1988; 82: 803-807
37 Radomski MW, Palmer RMJ, Moncada S. Characterization of the L-argi-nine: nitic oxide pathway in human platelets. Br J Heamatol 1990; 101: 325-328
38 Chen LY, Mehta JL. Inhibitory effect of high-density lipoprotein on platelet function is mediated by increase in nitric oxide synthase activity in platelets. Life Science 1994; 55: 1815-1821
39 Satoh K, Imaizumi TA, Yoshida H, Takamatsu S. High-density lipoprotein inhibits the production of platelet activating factor acetylhydrolase by HepG2 cells. J Clin Lab Med 1994; 124: 225-231
40 Sugatani J, Miwa M, Komiyama Y, Ito S. High-density lipoprotein inhibits the synthesis of platelet-activating factor in human vascular endothelial cells. J Lipid Mediat Cell Signal 1996; 13: 73-88
41 Surya II, Gorter G, Akkerman JW. Arachidonate transfer between platelets and lipoproteins. Thromb Haemost 1992; 68: 719-726