Increased Concentrations of Soluble CD40 Ligand, RANTES and GRO-α in Preeclampsia – Possible Role of Platelet Activation

Jan Roar Mellembakken; Nils Olav Solum; Thor Ueland; Vibeke Videm; Pål Aukrust

doi:10.1055/s-0037-1616061

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(05): 1272-1276
DOI: 10.1055/s-0037-1616061

Review Article

Schattauer GmbH

Increased Concentrations of Soluble CD40 Ligand, RANTES and GRO-α in Preeclampsia – Possible Role of Platelet Activation

Jan Roar Mellembakken

¹Department of Pediatric Research, Oslo

²Department of Obstetrics and Gynaecology, Oslo

,

Nils Olav Solum

³Research Institute of Internal Medicine, Oslo

,

Thor Ueland

³Research Institute of Internal Medicine, Oslo

⁴Section of Endocrinology, Oslo

,

Vibeke Videm

⁵Department of Immunology and Transfusion Medicine, Institute of Laboratory Medicine, Norwegian University of Science and Technology, Trondheim, Norway

,

Pål Aukrust

³Research Institute of Internal Medicine, Oslo

⁶Section of Clinical Immunology and Infectious Diseases, Medical Department, The National Hospital, University of Oslo, Oslo

› Author Affiliations

Abstract

Summary

Activated platelets may release inflammatory mediators that activate leukocytes and trigger inflammatory reactions in endothelial cells. We examined the concentrations of soluble CD40 ligand (sCD40L) and the chemokines RANTES and GRO-α in platelet-free plasma (PFP), and unstimulated and SFLLRN-stimulated platelet-rich plasma (PRP), as well as in platelet pellets before stimulation using enzyme immunoassays. Nineteen women with normal and twenty-one with preeclamptic pregnancies were studied, and several differences between these two groups of pregnancies were revealed (1). Women with preeclampsia had significantly increased concentrations of sCD40L and GRO-α in PFP (2). Platelets from these patients spontaneously released larger quantities of CD40L and RANTES ex vivo (3). When further activated ex vivo by SFLLRN, platelets from preeclamptic women released lower amounts per platelet of CD40L, RANTES and GRO-α (4). The platelet pellets in preeclamptic women contained decreased amounts of CD40L, RANTES and GRO-α per platelet. Our findings suggest enhanced platelet activation in vivo during preeclampsia resulting in increased release of inflammatory mediators, possibly contributing to inflammation, leukocyte activation and endothelial dysfunction in this disorder.

Keywords

Preeclampsia - platelets - CD40L - RANTES - GRO-α - SFLLRN

Full Text

References

References
1 Davey DA, MacGillivray I. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol 1988; 158: 892-8.
2 Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999; 180: 499-506.
3 Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol 1989; 161: 1200-4.
4 Roberts JM, Redman CWG. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 1993; 341: 1447-51.
5 Janes SL, Kyle PM, Redman C, Goodall AH. Flow cytometric detection of activated platelets in pregnant women prior to the development of preeclampsia. Thromb Haemost 1995; 74: 1059-63.
6 McKay DG, Goldenberg V, Kaunitz H, Csavossy I. Experimental eclampsia. An eelctron microscope study and review. Arch Pathol 1967; 84: 557-97.
7 Howie PW, Prentice CR, McNicol GP. Coagulation, fibrinolysis and platelet function in pre-eclampsia, essential hypertension and placental insufficiency. J Obstet Gynaecol Br Commonw 1971; 78: 992-1003.
8 Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Müller-Berghaus G, Kroczek RA. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-4.
9 Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines – CXC and CC chemokines. Adv Immunol 1994; 55: 97-179.
10 de Gaetano G, Evangelista V, Rajtar G, del Maschio A, Cerletti C. Activated polymorphnuclear leukocytes stimulate platelet function. Thromb Res 1990; XI Suppl 25-32.
11 Buhlmann JE, Noelle RJ. Therapeutic potential for blockade of the CD40 ligand, gp39. J Clin Immunol 1996; 16: 83-9.
12 Holme PA, M¸ller F, Solum NO, Brosstad F, Frøland SS, Aukrust P. Enhanced activation of platelets with abnormal release of RANTES in human immunodeficiency virus type 1 infection. FASEB J 1998; 12: 79-89.
13 Miga A, Masters S, Gonzalez M, Noelle RJ. The role of CD40-CD154 interactions in the regulation of cell mediated immunity. Immunol Invest 2000; 29: 111-4.
14 Aukrust P, Müller F, Ueland T, Berget T, Aaser E, Brunsvig A, Solum NO, Forfang K, Frøland SS, Gullestad L. Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina. Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes. Circulation 1999; 100: 614-20.
15 Slupsky JR, Kalbas M, Willuweit A, Henn V, Kroczek RA, Müller-Berghaus G. Activated platelets induce tissue factor expression on human umbilical vein endothelial cells by ligation of CD40. Thromb Haemost 1998; 80: 1008-14.
16 Bonnar J, McNicol GP, Douglas AS. Coagulation and fibrinolytic systems in pre-eclampsia and ecclampsia. BMJ 1971; 2: 12-6.
17 Athayde N, Romero R, Maymon E, Gomez R, Pacora P, Araneda H, Yoon BH. A role for the novel cytokine RANTES in pregnancy and parturition. Am J Obstet Gynecol 1999; 181: 989-94.
18 Cohen J, Ghezzi F, Romero R, Ghidini A, Mazor M, Tolosa JE, Goncalves LF, Gomez R. GRO alpha in the fetomaternal and amniotic fluid compartments during pregnancy and parturition. Am J Reprod Immunol 1996; 35: 23-9.
19 von Dadelszen P, Watson RW, Noorwali F, Marchall JC, Parado J, Farine D, Lye SJ, Ritchie JW, Rotstein OD. Maternal neutrophil apoptosis in normal pregnancy, preeclampsia, and normotensive intrauterine growth restriction. Am J Obstet Gynecol 1999; 181: 408-14.
20 Dunican AL, Leuenroth SJ, Ayala A, Simms HH. CXC chemokine suppression of polymorphonuclear leukocyte apoptosis and preservation of function is oxidative stress independent. Shock 2000; 13: 244-50.
21 Whigham KA, Howie PW, Drummond AH, Prentice CR. Abnormal platelet function in pre-eclampsia. Br J Obstet Gynaecol 1978; 85: 28-32.
22 Slupsky JR, Cawley JC, Kaplan C, Zuzel M. Analysis of CD9, CD32 and p67 signalling: use of degranulated platelets indicates direct involvement of CD9 and p67 in integrin activation. Br J Haematol 1997; 96: 275-86.
23 Michelson AD, Barnard MR, Hechtman HB, MacGregor H, Connolly RJ, Loscalzo J, Valeri CR. In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function. Proc Natl Acad Sci USA 1996; 93: 11877-82.
24 Lundahl TH, Petersson J, Fagerberg IH, Berg S, Lindahl TH. Impaired platelet function correlates with multi-organ dysfunction. Platelets 1998; 9: 223-5.
25 Damås JK, Gullestad L, Ueland T, Solum NO, Simonsen S, Frøland SS, Aukrust P. CXC-chemokines, a new group of cytokines in congestive heart failure – possible role of platelets and monocytes [see comments]. Cardiovasc Res 2000; 45: 428-36.
26 Weyrich AS, Elstad MR, McEver RP, McIntyre TM, Moore KL, Morrissey JH, Prescott SM, Zimmerman GA. Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 1996; 97: 1525-34.
27 Li N, Hu H, Lindqvist M, Wikström-Jonsson E, Goodall AH, Hjemdahl P. Platelet-leukocyte cross talk in whole blood. Arterioscler Thromb Vasc Biol 2000; 20: 2702-8.
28 Forlow SB, McEver RP, Nollert MU. Leukocyte-leukocyte interactions mediated by platelet microparticles under flow. Blood 2000; 95: 1317-23.
29 Clemetson KJ, Clemetson JM, Proudfoot AE, Power CA, Baggiolini M, Wells TN. Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets. Blood 2000; 96: 4046-54.
30 Greer IA, Haddad NG, Dawes J, Johnstone FD, Calder AA. Neutrophil activation in pregnancy-induced hypertension. Br J Obstet Gynaecol 1989; 96: 978-82.
31 Haeger M, Unander M, Norder-Hansson B, Tylman M, Bengtsson A. Complement, neutrophil and macrophage activation in women with severe preeclampsia and the syndrome of hemolysis, elevated liver enzymes and low platelet count. Obstet Gynecol 1992; 79: 19-26.