Pasteurella haemolytica in cattle produces fibrinohemorrhagic pleuropneumonia characterized by extensive pulmonary microvascular thrombosis and parenchymal necrosis. The purpose of this in vitro study was to determine if P. haemolytica lipopolysaccharide (LPS) promotes vascular thrombosis by inducing a procoagulant state in vascular endothelial cells. After treatment of confluent monolayers of bovine pulmonary artery endothelial cells with various concentrations of either P. haemolytica LPS or Escherichia coli LPS, the procoagulant activity of the endothelial cells was determined using a chromogenic assay dependent on cellular tissue factor expression. The LPS treatment induced significant increases in cellular tissue factor expression in a LPS concentration- and time-dependent manner. Highest levels of tissue factor were present at 22 hours after treatment, although high LPS concentrations induced moderate tissue factor levels at 5 hours after treatment. Interleukin-1 also induced tissue factor expression in endothelial cells and enhanced the LPS-induced effects. This interleukin-1 effect could be diminished by concurrent use of an interleukin-1 receptor antagonist. These results demonstrate that LPS and cytokine promotion of a procoagulant state in endothelial cells occurs in vitro. Similar mechanisms may play a role in P. haemolytica-mediated pulmonary vascular thrombosis.
AlexanderHRDohertyGMBureshCMVenzonDJNortonJA:
A recombinant human receptor antagonist to interleukin 1 improves survival after lethal endotoxemia in mice.
J Exp Med173:
1029–1032,
1991.
2.
ArendWPWelgusHGThompsonRCEisenbergSP:
Biological properties of recombinant human monocytederived interleukin 1 receptor antagonist.
J Clin Invest85:
1694–1697,
1990.
3.
BachRR:
Initiation of coagulation by tissue factor.
CRC Crit Rev Biochem23:
339–368,
1988.
4.
BevilacquaMPGimbroneMAJr:
Inducible endothelial functions in inflammation and coagulation.
Semin Thromb Hemostasis13:
425–433,
1987.
5.
BevilacquaMPPoberJSMajeauGRCotranRSGimbroneMAJr:
Interleukin I (IL-1) induces biosynthesis and cell surface expression of procoagulanl activity in human vascular endothelial cells.
J Exp Med160:
618–623,
1984.
6.
BevilacquaMPPoberJSMajeauGRFiersWCotranRSGimbroneMAJr:
Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1.
Proc Natl Acad Sci USA83:
4533–4537,
1986.
7.
BevilacquaMPPoberJSWheelerMECotranRSGimbroneMAJr:
Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion.
Am J Pathol121:
394–403,
1985.
BreiderMAWalkerRDHopkinsFMSchultzTWBowersockTL:
Pulmonary lesions induced by Pasteurella haemolytica in neutrophil sufficient and neutrophil deficient calves.
Can J Vet Res52:
205–209,
1988.
10.
CarBDSlausonDODoreMSuyemotoMM:
Endotoxin-mediated bovine alveolar macrophage procoagulant induction is dependent on protein kinase c activation.
Inflammation14:
681–689,
1990.
11.
ColucciMBalconiGLorenzetRPietraALocatiDDonatiMBSemeraroN:
Cultured human endothelial cells generate tissue factor in response to endotoxin.
J Clin Invest71:
1893–1896,
1983.
12.
CotranRS:
New roles for the endothelium in inflammation and immunity.
Am J Pathol129:
407–413,
1987.
13.
CrossmanDCCarrDPTuddenhamEGDPearsonJDMcVeyJH:
The regulation of tissue factor mRNA in human endothelial cells in response to endotoxin or phorbol ester.
J Biol Chem265:
9782–9787,
1990.
14.
CybulskyMIChanMKWMovatHZ:
Acute inflammation and microthrombosis induced by endotoxin, interleukin-1, and lumor necrosis factor and their implication in gram-negative infection.
Lab Invest58:
365–378,
1988.
15.
HannumCHWilcoxCJArendWPJoslinFGDrippsDJHeimdalPLArmesLGSommerAEisenbergSPThompsonRC:
Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor.
Nature343:
336–340,
1990.
McIntireFCSievertHWBarlowGHFinleyFALeeAY:
Chemical, physical, and biological properties of a lipopolysaccharide from Escherichia coli K-235.
Biochemistry6:
2363–2372,
1967.
18.
MooreKLAndreoliSPEsmonNLEsmonCTBangNU:
Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro.
J Clin Invest79:
124–130,
1987.
19.
MovatHZCybulskyMIColditzIGChanMKWDinarelloCA:
Acute inflammation in gram-negative infection: endotoxin, interleukin 1, tumor necrosis factor, and neutrophils.
Fed Proc46:
97–104,
1987.
20.
PaulsenDBMosierDAClinkenbeardKDConferAW:
Direct effects of Pasteurella haemolytica lipopolysaccharide on bovine endothelial cells in vitro.
Am J Vet Res50:
1633–1637,
1989.
21.
PohlmanTHHarlanJM:
Human endothelial cell response to lipopolysaccharide, interleukin-1, and tumor necrosis factor is regulated by protein synthesis.
Cell Immunol119:
41–52,
1989.
22.
RehmtullaAJThomsonRG:
A review of the lesions in shipping fever of cattle.
Can Vet J22:
1–8,
1981.
23.
RyanUS:
Immunofluorescence and immunocytochemistry of endothelial cell surface properties.
J Tissue Cult Methods10:
27–30,
1986.
24.
RyanUSMaxwellG:
Isolation, culture, and subculture of bovine pulmonary artery endothelial cells.
J Tissue Cult Methods10:
3–5,
1986.
25.
ScarpatiEMSadlerJE:
Regulation of endothelial cell coagulant properties modulation of tissue factor plasminogen activator inhibitors and thrombomodulin by phorbol 12-myristate 13-acetate and tumor necrosis factor.
J Biol Chem264:
20705–20713,
1989.
26.
SchreiberABWinklerMEDerynckR:
Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor.
Science232:
1250–1253,
1986.
SharmaSAOlchowyTWJBreiderMA:
Alveolar macrophage and neutrophil interactions in Pasteurella haemolytica induced endothelial cell injury.
J Infect Dis165:
651–657,
1992.
29.
SlocombeREMalarkJIngersollRTDerksenFJRobinsonNE:
Importance of neutrophils in the pathogenesis of acute pneumonic pasteurellosis in calves.
Am J Vet Res46:
2253–2258,
1985.
30.
SurprenantYMZuckermanSH:
A novel microtiter plate assay for the quantitation of procoagulant activity on adherent monocytes, macrophage and endothelial cells.
Thromb Res53:
339–346,
1989.
31.
UlichTRYinSGuoKdel CastilloJEisenbergSPThompsonRC:
The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation.
Am J Pathol138:
521–524,
1991.
32.
WakabayashiGGelfandJABurkeJFThompsonRCDinarelloCA:
A specific receptor antagonist for interleukin 1 prevents Escherichia coli-induced shock in rabbits.
Fed Am Soc Exp Biol5:
338–343,
1991.
33.
WharramBLFittingKKunkelSLRemickDGMerrittSEWigginsRC:
Tissue factor expression in endothelial cell/monocyte cocultures stimulated by lipopolysaccharide and/or aggregated IgG. Mechanisms of cell:cell communication.
J Immunol146:
1437–1445,
1991.
34.
WhiteleyLOMaheswaranSKWeissDJAmesTR:
Immunohistochemical localization of Pasteuretta haemolytica A1-derived endotoxin, leukotoxin, and capsular polysaccharide in experimental bovine Pasteurella pneumonia.
Vet Pathol27:
150–161,
1990.
35.
WhiteleyLOMaheswaranSKWeissDJAmesTR:
The morphologic and hematologic alterations caused by intratracheal inoculation of live and ultraviolet light-killed Pasteurella haemolytica A1 in calves.
Vet Pathol28:
275–285,
1991.
36.
WhiteleyLOMaheswaranSKWeissDJAmesTR:
Pasteurella haemolytica A1 and bovine respiratory disease: pathogenesis.
J Vet Intern Med6:
11–22,
1992.
