Endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species

Christopher J. Kuckleburg; Raksha Tiwari; Charles J. Czuprynski

doi:10.1160/TH07-07-0474

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(02): 363-372
DOI: 10.1160/TH07-07-0474

Endothelium and Vascular Development

Schattauer GmbH

Endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species

Christopher J. Kuckleburg

¹Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA

,

Raksha Tiwari

¹Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA

,

Charles J. Czuprynski

¹Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA

› Author Affiliations

Abstract

Summary

A common feature of severe sepsis is vascular inflammation and damage to the endothelium. Because platelets can be directly activated by bacteria and endotoxin, these cells may play an important role in determining the outcome of sepsis. For example, inhibiting platelet interactions with the endothelium has been shown to attenuate endothelial cell damage and improve survival during sepsis. Although not entirely understood, the interactions between bacteria-activated platelets and the endothelium may play a key role in the vascular pathology of bacterial sepsis. Haemophilus somnus is a bacterial pathogen that causes diffuse vascular inflammation and endothelial damage. In some cases H.somnus infection results in an acute and fatal form of vasculitis in the cerebral microvasculature known as thrombotic meningoencephalitis (TME). In this study, we have characterized the mechanisms involved in endothelial cell apoptosis induced by activated platelets. We observed that direct contact between H.somnus-activated platelets and endothelial cells induced significant levels of apoptosis; however, Fas receptor activation on bovine endothelial cells was not able to induce apoptosis unless protein synthesis was disrupted. Endothelial cell apoptosis by H.somnus-activated platelets required activation of both caspase-8 and caspase-9, as inhibitors of either caspase inhibited apoptosis. Furthermore, activated platelets induced endothelial cell production of reactive oxygen species (ROS) and disrupting ROS activity in endothelial cells significantly inhibited apoptosis. These findings suggest that bacterial activation of platelets may contribute to endothelial cell dysfunction observed during sepsis, specifically by inducing endothelial cell apoptosis.

Keywords

Histophilus - FasL - ROS - TNFα - Haemophilus somnus

Full Text

References

References
1 Henn V, Slupsky JR, Grafe M. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 39: 591-594.
2 Ahmad R, Menezes J, Knafo L. et al. Activated human platelets express Fas-L and induce apoptosis in Fas-positive tumor cells. J Leukoc Biol 2001; 69: 123-128.
3 Hsu-Lin S, Berman CL, Furie BC. et al. A platelet membrane protein expressed during platelet activation and secretion. Studies using a monoclonal antibody specific for thrombin-activated platelets. J Biol Chem 1984; 259: 9121-9126.
4 McEver RP, Martin MN. A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem 1984; 259: 9799-9804.
5 Cognasse F, Hamzeh H, Chavarin P. et al. Evidence of Toll-like receptor molecules on human platelets. Immun Cell Biol 2005; 83: 196-198.
6 Stahl AL, Svensson M, Morgelin M. et al. Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome. Blood 2006; 108: 167-176.
7 Aslam R, Speck ER, Kim M. et al. Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factoralpha production in vivo. Blood 2006; 107: 637-641.
8 Clark SR, Ma AC, Tavener SA. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nature Med 2007; 13: 463-469.
9 Andrews JJ, Anderson TD, Slife LN. et al. Microscopic lesions associated with the isolation of Haemophilus somnus from pneumonic bovine lungs. Vet Pathol 1985; 22: 131-136.
10 Gogolewski RP, Leathers CW, Liggitt HD. et al. Experimental Haemophilus somnus pneumonia in calves and immunoperoxidase localization of bacteria. Vet Pathol 1987; 24: 250-256.
11 Harris FW, Janzen ED. The Haemophilus somnus disease complex (Haemophilosis): A review. Can Vet J 1984; 30: 816-822.
12 Pritchard DG, Shreeve J, Bradley R. The experimental infection of calves with a British strain of Haemophilus somnus . Res Vet Sci 1979; 26: 7-11.
13 Kuckleburg CJ, Sylte MJ, Inzana TJ. et al. Bovine platelets activated by Haemophilus somnus and its LOS induce apoptosis in bovine endothelial cells. Microb Pathog 2005; 38: 23-32.
14 Sylte MJ, Corbeil LB, Inzana TJ. et al. Haemophilus somnus induces apoptosis in bovine endothelial cells in vitro. Infect Immun 2001; 69: 1650-1660.
15 Inzana TJ, Iritani B, Gogolewski RP. et al. Purification and characterization of lipooligosaccharides from four strains of „Haemophilus somnus”. Infect Immun 1988; 56: 2830-2837.
16 Inzana TJ, Hensley J, McQuiston J. et al. Phase variation and conservation of lipooligosaccharide epitopes in Haemophilus somnus . Infect Immun 1997; 65: 4675-4681.
17 Kuckleburg CJ, McClenahan DJ, Czuprynski CJ. Platelet activation by Histophilus somni and its lipooligosacharride induces endothelial cell proinflammatory responses and platelet internalization. Shock. 2007 epub ahead of print.
18 Margalit KA, Cowan RG, Harman RM. et al. Apoptosis of bovine ovarian surface epithelial cells by Fas antigen/Fas ligand signaling. Reproduction 2005; 130: 751-758.
19 Hayakawa A, Wu J, Kawamoto Y. et al. Activation of caspase-8 is critical for sensitivity to cytotoxic anti-Fas antibody-induced apoptosis in human ovarian cancer cells. Apoptosis 2002; 7: 107-113.
20 Urbich C, Dernbach E, Aicher A. et al. CD40 ligand inhibits endothelial cell migration by increasing production of endothelial reactive oxygen species. Circulation 2002; 106: 981-986.
21 Gorog P, Pearson JD, Kakkar VV. Generation of reactive oxygen metabolites by phagocytosing endothelial cells. Atherosclerosis 1988; 72: 19-27.
22 Zhao L, Ohtaki Y, Yamaguchi K. et al. LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system. Blood 2002; 100: 3233-3239.
23 Danese S, de la Motte C, Sturm A. et al. Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients. Gastroenterology 2003; 124: 1249-1264.
24 Marcondes S, Lafay M, Brohard-Bohn B. et al. Platelets induce human umbilical vein endothelial cell proliferation through P-selectin. Life Sci 2000; 66: 1817-1826.
25 Sindram D, Porte RJ, Hoffman MR. et al. Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver. Gastroenterology 2000; 118: 183-191.
26 Sindram D, Porte RJ, Hoffman MR. et al. Synergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: a Kupffer cell-mediated injury. Faseb J 2001; 15: 1230-1232.
27 Wassmer SC, de Souza JB, Frere C. et al. TGFbeta1 released from activated platelets can induce TNFstimulated human brain endothelium apoptosis: a new mechanism for microvascular lesion during cerebral malaria. J Immunol 2006; 176: 1180-1184.
28 Janiszewski M, Do Carmo AO, Pedro MA. et al. Platelet-derived exosomes of septic individuals possess proapoptotic NAD(P)H oxidase activity: A novel vascular redox pathway. Crit Care Med 2004; 32: 818-825.
29 Eipel C, Bordel R, Nickels RM. et al. Impact of leukocytes and platelets in mediating hepatocyte apoptosis in a rat model of systemic endotoxemia. Am J Physiol Gastrointest Liver Physiol 2004; 286: G769-776.
30 da Costa Martins P, van den Berk N, Ulfman LH. et al. Platelet-monocyte complexes support monocyte adhesion to endothelium by enhancing secondary tethering and cluster formation. Arterioscler Thromb Vasc Biol 2004; 24: 193-199.
31 Pitchford SC, Yano H, Lever R. et al. Platelets are essential for leukocyte recruitment in allergic inflammation. J Allergy Clin Immunol 2003; 112: 109-118.
32 Sun G, Chang WL, Li J. et al. Inhibition of platelet adherence to brain microvasculature protects against severe Plasmodium berghei malaria. Infect Immun 2003; 71: 6553-6561.
33 Longo CR, Arvelo MB, Patel VI. et al. A20 protects from CD40-CD40 ligand-mediated endothelial cell activation and apoptosis. Circulation 2003; 108: 1113-1118.
34 Lee JK, Seki N, Sayers TJ. et al. Constitutive expression of functional CD40 on mouse renal cancer cells: induction of Fas and Fas-mediated killing by CD40L. Cell Immunol 2005; 235: 145-152.
35 Chu P, Deforce D, Pedersen IM. et al. Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99: 3854-3859.
36 Eliopoulos AG, Davies C, Knox PG. et al. CD40 induces apoptosis in carcinoma cells through activation of cytotoxic ligands of the tumor necrosis factor superfamily. Mol Cell Biol 2000; 20: 5503-5515.
37 Papathanassoglou ED, Moynihan JA, McDermott MP. et al. Expression of Fas (CD95) and Fas ligand on peripheral blood mononuclear cells in critical illness and association with multiorgan dysfunction severity and survival. Crit Care Med 2001; 29: 709-718.
38 Perl M, Chung CS, Lomas-Neira J. et al. Silencing of Fas, but not caspase-8, in lung epithelial cells ameliorates pulmonary apoptosis, inflammation, and neutrophil influx after hemorrhagic shock and sepsis. Am J Pathol 2005; 167: 1545-1559.
39 Ayala A, Lomas JL, Grutkoski PS. et al. Fas-ligand mediated apoptosis in severe sepsis and shock. Scand J Infect Dis 2003; 35: 593-600.
40 Li JH, Kluger MS, Madge LA. et al. Interferongamma augments CD95(APO-1/Fas) and pro-caspase-8 expression and sensitizes human vascular endothelial cells to CD95-mediated apoptosis. Am J Pathol 2002; 161: 1485-1495.
41 Lou J, Donati YR, Juillard P. et al. Platelets play an important role in TNF-induced microvascular endothelial cell pathology. Am J Pathol 1997; 151: 1397-1405.
42 Deleault KM, Skinner SJ, Brooks SA. Tristetraprolin regulates TNF TNF-alpha mRNA stability via a proteasome dependent mechanism involving the combined action of the ERK and p38 pathways. Mol Immun 2008; 45: 13-24.
43 Rajasingh J, Bord E, Luedemann C. et al. IL-10-induced TNF-alpha mRNA destabilization is mediated via IL-10 suppression of p38 MAP kinase activation and inhibition of HuR expression. Faseb J 2006; 20: 2112-2114.
44 Hamilton TA, Novotny M, Datta S. et al. Chemokine and chemoattractant receptor expression: posttranscriptional regulation. J Leukoc Biol 2007; 82: 213-219.
45 Shakibaei M, Schulze-Tanzil G, Takada Y. et al. Redox regulation of apoptosis by members of the TNF superfamily. Antioxid Redox Signal 2005; 7: 482-496.
46 Garrido C, Galluzzi L, Brunet M. et al. Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 2006; 13: 1423-1433.
47 Spanaus KS, Schlapbach R, Fontana A. TNF-alpha and IFN-gamma render microglia sensitive to Fas ligand-induced apoptosis by induction of Fas expression and down-regulation of Bcl-2 and Bcl-xL. Eur J Immunol 1998; 28: 4398-4408.
48 Scaffidi C, Fulda S, Srinivasan A. et al. Two CD95 (APO-1/Fas) signaling pathways. Embo J 1998; 17: 1675-1687.
49 Scaffidi C, Schmitz I, Zha J. et al. Differential modulation of apoptosis sensitivity in CD95 type I and type II cells. J Biol Chem 1999; 274: 22532-22538.
50 Barnhart BC, Alappat EC, Peter ME. The CD95 type I/type II model. Semin Immunol 2003; 15: 185-193.
51 Nagata S. Biddable death. Nat Cell Biol 1999; 1: E143-145.
52 Azevedo LC, Janiszewski M, Pontieri V. et al. Platelet-derived exosomes from septic shock patients induce myocardial dysfunction. Crit Care 2007; 11: R120.
53 Bombeli T, Schwartz BR, Harlan JM. Endothelial cells undergoing apoptosis become proadhesive for nonactivated platelets. Blood 1999; 93: 3831-3838.