Abstract
Endothelial cells (EC) synthesize platelet-activating factor (PAF) when activated by agents such as ATP or thrombin, and PAF production occurs as a consequence of endothelial phospholipase A activity. Because interactions between Rickettsia prowazekii and a variety of host cells result in the expression of phospholipase A activity, we assessed the relative abilities of uninfected and rickettsia-infected EC to synthesize PAF. Endothelial cells were infected with rickettsiae and examined at 24-h intervals for rickettsial multiplication, EC viability, and PAF synthesis. By 24 h postinfection, 80% of the EC were infected with an average of 10.6 rickettsiae per cell; by 72 h, the rickettsiae were too numerous to count and the numbers of viable EC began to decrease. Both rickettsia-infected and sham-treated EC synthesized PAF when stimulated with either thrombin or ATP, but rickettsia-infected EC synthesized about three times as much PAF in response to cell activation as did their uninfected counterparts. Additionally, unlike their uninfected counterparts, rickettsia-infected EC synthesized significant amounts of PAF in the absence of cell activation; rickettsia-infected EC synthesized as much PAF in the absence of activation as did uninfected EC in response to ATP. In each case, essentially all of the newly synthesized PAF remained with the cell pellet. Finally, EC incubated with high numbers of rickettsiae (1,000 rickettsiae per EC) for 30 min synthesized more PAF when activated with ATP than did their sham-treated activated counterparts.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anggård E. E. The endothelium--the body's largest endocrine gland? J Endocrinol. 1990 Dec;127(3):371–375. doi: 10.1677/joe.0.1270371. [DOI] [PubMed] [Google Scholar]
- BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
- BOVARNICK M. R., MILLER J. C., SNYDER J. C. The influence of certain salts, amino acids, sugars, and proteins on the stability of rickettsiae. J Bacteriol. 1950 Apr;59(4):509–522. doi: 10.1128/jb.59.4.509-522.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fajardo L. F. The complexity of endothelial cells. A review. Am J Clin Pathol. 1989 Aug;92(2):241–250. doi: 10.1093/ajcp/92.2.241. [DOI] [PubMed] [Google Scholar]
- GIMENEZ D. F. STAINING RICKETTSIAE IN YOLK-SAC CULTURES. Stain Technol. 1964 May;39:135–140. doi: 10.3109/10520296409061219. [DOI] [PubMed] [Google Scholar]
- Graybill J. R., Hawiger J., Des Prez R. M. Complement and coagulation in Rocky Mountain spotted fever. South Med J. 1973 Apr;66(4):410–413. doi: 10.1097/00007611-197304000-00003. [DOI] [PubMed] [Google Scholar]
- Heller R., Bussolino F., Ghigo D., Garbarino G., Schröder H., Pescarmona G., Till U., Bosia A. Protein kinase C and cyclic AMP modulate thrombin-induced platelet-activating factor synthesis in human endothelial cells. Biochim Biophys Acta. 1991 Jun 7;1093(1):55–64. doi: 10.1016/0167-4889(91)90138-n. [DOI] [PubMed] [Google Scholar]
- Jaffe E. A. Cell biology of endothelial cells. Hum Pathol. 1987 Mar;18(3):234–239. doi: 10.1016/s0046-8177(87)80005-9. [DOI] [PubMed] [Google Scholar]
- Jaffe E. A., Hoyer L. W., Nachman R. L. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest. 1973 Nov;52(11):2757–2764. doi: 10.1172/JCI107471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanse S. M., Takahashi K., Lam H. C., Rees A., Warren J. B., Porta M., Molinatti P., Ghatei M., Bloom S. R. Cytokine stimulated endothelin release from endothelial cells. Life Sci. 1991;48(14):1379–1384. doi: 10.1016/0024-3205(91)90434-d. [DOI] [PubMed] [Google Scholar]
- Kucey D. S., Kubicki E. I., Rotstein O. D. Platelet-activating factor primes endotoxin-stimulated macrophage procoagulant activity. J Surg Res. 1991 May;50(5):436–441. doi: 10.1016/0022-4804(91)90021-d. [DOI] [PubMed] [Google Scholar]
- Libby P., Ordovas J. M., Auger K. R., Robbins A. H., Birinyi L. K., Dinarello C. A. Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. Am J Pathol. 1986 Aug;124(2):179–185. [PMC free article] [PubMed] [Google Scholar]
- Manor E., Sarov I. Tumor necrosis factor alpha and prostaglandin E2 production by human monocyte-derived macrophages infected with spotted fever group rickettsiae. Ann N Y Acad Sci. 1990;590:157–167. doi: 10.1111/j.1749-6632.1990.tb42218.x. [DOI] [PubMed] [Google Scholar]
- McIntyre T. M., Zimmerman G. A., Satoh K., Prescott S. M. Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate. J Clin Invest. 1985 Jul;76(1):271–280. doi: 10.1172/JCI111957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mueller H. W., O'Flaherty J. T., Wykle R. L. Biosynthesis of platelet activating factor in rabbit polymorphonuclear neutrophils. J Biol Chem. 1983 May 25;258(10):6213–6218. [PubMed] [Google Scholar]
- NEVA F. A., SNYDER J. C. Studies on the toxicity of typhus rickettsiae. I. Susceptibility of the white rat, with a note on pathologic changes. J Infect Dis. 1952 Jul-Aug;91(1):72–78. doi: 10.1093/infdis/91.1.72. [DOI] [PubMed] [Google Scholar]
- NEVA F. A., SNYDER J. C. Studies on the toxicity of typhus rickettsiae. III. Observations on the mechanism of toxic death in white mice and white rats. J Infect Dis. 1955 Jul-Aug;97(1):73–87. doi: 10.1093/infdis/97.1.73. [DOI] [PubMed] [Google Scholar]
- Ody C. Profile of prostaglandin (PG) production by endothelial cells. Curr Probl Clin Biochem. 1983;13:108–115. [PubMed] [Google Scholar]
- PARKER F., Jr, NEVA F. A. Studies on the toxicity of typhus rickettsiae. II. Pathologic findings in white rats and white mice. Am J Pathol. 1954 Mar-Apr;30(2):215–237. [PMC free article] [PubMed] [Google Scholar]
- Prescott S. M., Zimmerman G. A., McIntyre T. M. Human endothelial cells in culture produce platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with thrombin. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3534–3538. doi: 10.1073/pnas.81.11.3534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raoult D., Drancourt A. M., Ardissone J. P. Enzyme secretion by human endothelial cells infected with Rickettsia conorii. Acta Virol. 1987 Aug;31(4):352–356. [PubMed] [Google Scholar]
- SNYDER J. C., BOVARNICK M. R., MILLER J. C., CHANG R. S. M. Observations on the hemolytic properties of typhus rickettsiae. J Bacteriol. 1954 Jun;67(6):724–730. doi: 10.1128/jb.67.6.724-730.1954. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scarpati E. M., Sadler J. E. 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 Chem. 1989 Dec 5;264(34):20705–20713. [PubMed] [Google Scholar]
- Silberman R., Fiset P. Method for counting Rickettsiae and Chlamydiae in purified suspensions. J Bacteriol. 1968 Jan;95(1):259–261. doi: 10.1128/jb.95.1.259-261.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sporn L. A., Shi R. J., Lawrence S. O., Silverman D. J., Marder V. J. Rickettsia rickettsii infection of cultured endothelial cells induces release of large von Willebrand factor multimers from Weibel-Palade bodies. Blood. 1991 Nov 15;78(10):2595–2602. [PubMed] [Google Scholar]
- Stern D. M., Kaiser E., Nawroth P. P. Regulation of the coagulation system by vascular endothelial cells. Haemostasis. 1988;18(4-6):202–214. doi: 10.1159/000215808. [DOI] [PubMed] [Google Scholar]
- Stremler K. E., Stafforini D. M., Prescott S. M., McIntyre T. M. Human plasma platelet-activating factor acetylhydrolase. Oxidatively fragmented phospholipids as substrates. J Biol Chem. 1991 Jun 15;266(17):11095–11103. [PubMed] [Google Scholar]
- Turco J., Winkler H. H. Differentiation between virulent and avirulent strains of Rickettsia prowazekii by macrophage-like cell lines. Infect Immun. 1982 Mar;35(3):783–791. doi: 10.1128/iai.35.3.783-791.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WATTENBERG L. W., ELISBERG B. L., WISSEMAN C. L., Jr, SMADEL J. E. Studies of rickettsial toxins. II. Altered vascular physiology in rickettsial toxemia of mice. J Immunol. 1955 Feb;74(2):147–157. [PubMed] [Google Scholar]
- WISSEMAN C. L., Jr, JACKSON E. B., HAHN F. E., LEY A. C., SMADEL J. E. Metabolic studies of rickettsiae. I. The effects of antimicrobial substances and enzyme inhibitors on the oxidation of glutamate by purified rickettsiae. J Immunol. 1951 Aug;67(2):123–136. [PubMed] [Google Scholar]
- Walker D. H., Firth W. T., Ballard J. G., Hegarty B. C. Role of phospholipase-associated penetration mechanism in cell injury by Rickettsia rickettsii. Infect Immun. 1983 May;40(2):840–842. doi: 10.1128/iai.40.2.840-842.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker D. H., Firth W. T., Edgell C. J. Human endothelial cell culture plaques induced by Rickettsia rickettsii. Infect Immun. 1982 Jul;37(1):301–306. doi: 10.1128/iai.37.1.301-306.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker D. H., Mattern W. D. Rickettsial vasculitis. Am Heart J. 1980 Dec;100(6 Pt 1):896–906. doi: 10.1016/0002-8703(80)90072-1. [DOI] [PubMed] [Google Scholar]
- Walker T. S., Brown J. S., Hoover C. S., Morgan D. A. Endothelial prostaglandin secretion: effects of typhus rickettsiae. J Infect Dis. 1990 Nov;162(5):1136–1144. doi: 10.1093/infdis/162.5.1136. [DOI] [PubMed] [Google Scholar]
- Walker T. S., Dersch M. W., White W. E. Effects of typhus rickettsiae on peritoneal and alveolar macrophages: rickettsiae stimulate leukotriene and prostaglandin secretion. J Infect Dis. 1991 Mar;163(3):568–573. doi: 10.1093/infdis/163.3.568. [DOI] [PubMed] [Google Scholar]
- Walker T. S., Hoover C. S. Rickettsial effects on leukotriene and prostaglandin secretion by mouse polymorphonuclear leukocytes. Infect Immun. 1991 Jan;59(1):351–356. doi: 10.1128/iai.59.1.351-356.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker T. S., Triplett D. A., Javed N., Musgrave K. Evaluation of lupus anticoagulants: antiphospholipid antibodies, endothelium associated immunoglobulin, endothelial prostacyclin secretion, and antigenic protein S levels. Thromb Res. 1988 Aug 1;51(3):267–281. doi: 10.1016/0049-3848(88)90104-1. [DOI] [PubMed] [Google Scholar]
- Walker T. S., Winkler H. H. Penetration of cultured mouse fibroblasts (L cells) by Rickettsia prowazeki. Infect Immun. 1978 Oct;22(1):200–208. doi: 10.1128/iai.22.1.200-208.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker T. S., Winkler H. H. Rickettsial hemolysis: rapid method for enumeration of metabolically active typhus rickettsiae. J Clin Microbiol. 1979 May;9(5):645–647. doi: 10.1128/jcm.9.5.645-647.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watanabe M., Yagi M., Omata M., Hirasawa N., Mue S., Tsurufuji S., Ohuchi K. Stimulation of neutrophil adherence to vascular endothelial cells by histamine and thrombin and its inhibition by PAF antagonists and dexamethasone. Br J Pharmacol. 1991 Jan;102(1):239–245. doi: 10.1111/j.1476-5381.1991.tb12160.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weksler B. B., Ley C. W., Jaffe E. A. Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and the ionophore A 23187. J Clin Invest. 1978 Nov;62(5):923–930. doi: 10.1172/JCI109220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whatley R. E., Zimmerman G. A., McIntyre T. M., Prescott S. M. Endothelium from diverse vascular sources synthesizes platelet-activating factor. Arteriosclerosis. 1988 May-Jun;8(3):321–331. doi: 10.1161/01.atv.8.3.321. [DOI] [PubMed] [Google Scholar]
- Whatley R. E., Zimmerman G. A., McIntyre T. M., Prescott S. M. Lipid metabolism and signal transduction in endothelial cells. Prog Lipid Res. 1990;29(1):45–63. doi: 10.1016/0163-7827(90)90005-6. [DOI] [PubMed] [Google Scholar]
- Winkler H. H., Daugherty R. M. Phospholipase A activity associated with the growth of Rickettsia prowazekii in L929 cells. Infect Immun. 1989 Jan;57(1):36–40. doi: 10.1128/iai.57.1.36-40.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winkler H. H. Early events in the interaction of the obligate intracytoplasmic parasite, Rickettsia prowazekii, with eucaryotic cells: entry and lysis. Ann Inst Pasteur Microbiol. 1986 May-Jun;137A(3):333–336. doi: 10.1016/s0769-2609(86)80044-8. [DOI] [PubMed] [Google Scholar]
- Winkler H. H. Inhibitory and restorative effects of adenine nucleotides on rickettsial adsorption and hemolysis. Infect Immun. 1974 Jan;9(1):119–126. doi: 10.1128/iai.9.1.119-126.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winkler H. H., Miller E. T. Activated complex of L-cells and Rickettsia prowazekii with N-ethylmaleimide-insensitive phospholipase A. Infect Immun. 1984 Sep;45(3):577–581. doi: 10.1128/iai.45.3.577-581.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winkler H. H., Miller E. T. Phospholipase A activity in the hemolysis of sheep and human erythrocytes by Rickettsia prowazeki. Infect Immun. 1980 Aug;29(2):316–321. doi: 10.1128/iai.29.2.316-321.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winkler H. H., Miller E. T. Phospholipase A and the interaction of Rickettsia prowazekii and mouse fibroblasts (L-929 cells). Infect Immun. 1982 Oct;38(1):109–113. doi: 10.1128/iai.38.1.109-113.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wisseman C. L., Jr, Waddell A. D., Walsh W. T. In vitro studies of the action of antibiotics on Rickettsia prowazeki by two basic methods of cell culture. J Infect Dis. 1974 Dec;130(6):564–574. doi: 10.1093/infdis/130.6.564. [DOI] [PubMed] [Google Scholar]
- Yamada T., Harber P., Pettit G. W., Wing D. A., Oster C. N. Activation of the kallikrein-kinin system in Rocky Mountain spotted fever. Ann Intern Med. 1978 Jun;88(6):764–768. doi: 10.7326/0003-4819-88-6-764. [DOI] [PubMed] [Google Scholar]
- de Brito T., Hoshino-Shimizu S., Pereira M. O., Rigolon N. The pathogenesis of the vascular lesions in experimental rickettsial disease of the guinea pig (Rocky Mountain Spotted fever group). A light, immunofluorescent and electron microscopic study. Virchows Arch A Pathol Pathol Anat. 1973;358(3):205–214. doi: 10.1007/BF00543228. [DOI] [PubMed] [Google Scholar]
