rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2003-1353rsp-1217Research ArticleСтатьиArticlesС-реактивный белок удлиняет время свертывания крови в фосфолипид-зависимых коагуляционных тестахC-reactive protein prolongs blood coagulation time in phospholipids-dependent coagulation testsKozminL DKozminL D-MartinovA IMartinovA I-LisitsinaT ALisitsinaT A-РешетнякТ. М.ReshetnyakT M-LaugaV. I.LaugaV. I.-BliznukovO PBliznukovO P-200315062003413№3 (2003)1620Copyright © Kozmin L.D., Martinov A.I., Lisitsina T.A., Решетняк Т.М., Lauga V.I., Bliznukov O.P., 20032003Kozmin L.D., Martinov A.I., Lisitsina T.A., Решетняк Т.М., Lauga V.I., Bliznukov O.P.Kozmin L.D., Martinov A.I., Lisitsina T.A., Reshetnyak T.M., Lauga V.I., Bliznukov O.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/1217

Цель. Изучить влияние различных форм СРВ на время свертывания крови в стандартных фос- фодипид-зависимых коагуляционных тестах. Материалы и методы. К плазме здоровых доноров добавляли вьсокоочищенные нативный СРВ и мономерный СРВ (0 - 1,6 мкМ). а также комплексы нативного СРВ и моноспецифических кроличьих антител к нему (1,6 мкМ). Время свертывания плазмы крови с СРВ регистрировали с помощью оптического коагулометра в фосфолипид-зависимых коагуляционных тестах про- тромбинового времени, активированного частичного тромбопластинового времени, каолинового времени, времени эллаговой кислоты и теста яда гадюки Рассела. Результаты. Нативный СРВ способен удлинять время свертывания крови во всех перечисленных коагуляционных тестах, за исключением протромбинового времени. Влияние СРВ на время свертывания крови в этих теггах имеет характер концентрационной зависимости, при этом специфические антитела к нативному СРВ не ингибируют действие белка на время свертывания крови. Мономерный СРВ в диапазоне концентраций 0-1,6 мкМ не влияет на свертывание крови в фосфолипид-зависимых коагуляционных тестах. Заключение. Нативный СРВ при высоком содержании в плазме крови (более 0,4 мкМ) проявляет свойства естественного антикоагулянта в фосфолипид-зависимых коагуляционных тестах in vitro.

C-refctive protein prolongs blood coagulation time in phospholipids-dependent coagulation tests. O.P. Bliznukov, L.D. Kostin, A.J. Martinov, T.A. Lisitsina, T.M. Reshetnyak, V.J. Lauga Objective. To study influence of different CRP forms on blood clotting time in standard phospholipid clotting tests. Material and methods. Purified native CRP. monomeric CRP (0-1.6 M), immune complexes of native CRP and rabbit polyclonal anti-CRP antibodies (1.6 M) were added to blood plasma of healthy donors. Blood clotting time was registered using optical coagulometer. Phospholipid dependent prothrombin time (PT), activated partial tromboplastin time (APTT), kaolin clotting time (KCT) with kaolin and ellagic acid, dilute Russel viper venom time (dRVVT) were determined. Results. Native CRP was able to increase blood clotting time in all mentioned clotting tests, excluding prothrombin time. CRP influence on blood clotting time showed a concentration dependence. Polyclonal rabbit anti-CRP antibodies had no inhibitory effect on CRP prolonged blood clotting time. Monomeric CRP (0-1.6 M) had no influence on blood clotting time in all phospholipid-dependent clotting tests.

С-реактивный белок (СРВ)фосфолипид-зависимые коагуляционные тестыC-reactive proteinphospholipid-dependent dotting testsReferences<div><p>Полевщиков А.В., Назаров П.Г. Роль С-реактивного белка и сывороточного амилоидного протеина А в иммунорегуляции. Иммунология, 1993, 4, 6-10.</p><p>Pepys М.В,Baltz M.L. Acute phase proteins with special reference to C-reactive protein and related proteins (pen- taxins) and seruni amyloid A protein. Adv. Immunol., 1983, 34, 141-212.</p><p>Borque L., Bellod L., Rus A. et al. Development and validation of an automated and ultrasensitive immunoturbidi- metric assay for C-reactive protein. Clin. Chem., 2000,46, 1839-1842.</p><p>Hutchinson W., Koenig W., Frohlich M. Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population. Clin. Chem., 2000. 46, 934-938.</p><p>Macy E.M., Hayes T.E., Tracy R.P. Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications.Clin. Chem., 1997,43, 52-58.</p><p>Macintyre S., Samols D., Dailey P.et al. Two car- boxylesterases bind C-reactive protein within the endoplasmic reticulum and regulate its secretion during the acute phase response.J. Biol. Chem., 1994, 269, 24496-24503.</p><p>Peltoia H., Rasanen J.A. C-reactive protein in rapid differentiation of acute epiglottitis from spasmodic croup and acute laryngotracheitis: a preliminary report. J. Pediatr., 1983, 102, 713-715.</p><p>Peltoia H„ Holmberg C. Rapidity of C-reactive protein in detecting potential septicemia. Pediatr. Infect. Dis., 1983,2. 374-376.</p><p>Maseri A. Inflammation, atherosclerosis, and ischemic events - exploring the hidden side of the moon. N.Engl. J. Med., 1997, 336. 1014-1016.</p><p>Peltoia H., Vahvanen V., Alto K. Fever, C-reactive protein, and erythrocyte sedimentation rate in monitoring recovery from septic arthritis: a preliminary study. J. Pediatr. Orthop., 1984, 4, 170-174.</p><p>Sharif М, Shepstone L., Elson C.J. et al. Increased serum C-reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee, Ann. Rheum. Dis., 2000, 59, 71-74.</p><p>Bataille R., Boccadoro М., Klein B. et al. C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. Blood, 1992, 80, 733-737.</p><p>Francis J.L. Laboratory investigation of hypercoagulability. Semin. Thromb. Hemost., 1998,24, 111-126.</p><p>Bick R.L. Coagulation abnormalities in malignancy: a review. Semin. Thromb. Hemost., 1992, 18, 353-372.</p><p>Zwaal R.F., Comfurius P., Bevers E.M. Lipid-protein interactions in blood coagulation. Biochim, Biophy. Acta, 1998, 1376, 433-453.</p><p>Oliveira E.B., Gotschlich E.C., Liu T.Y. Comparative studies on the binding properties of human and rabbit C-reactive proteins. J. Immunol., 1980, 124, 1396-1402.</p><p>Sui S., Sun Y., Mi L. Calcium-dependent binding of rabbit C-reactive protein to supported lipid monolayers containing exposed phosphorylcholine group. Biophys. J., 1999, 76, 333-341.</p><p>Pepys M.B., Rowe I.F., Baltz M. C-reactive protein: binding to lipids and lipoproteins. Int. Rev. Exp. Pathol., 1985, 27, 83-111.</p><p>de Beer F.C., Soutar A.K., Baltz M.L. Low density lipoprotein and very low density lipoprotein are selectively bound by aggregated C-reactive protein. J. Exp. Med., 1982, 156, 230-242.</p><p>Narkates A.J., Voianakis J.E. C-reactive protein binding specificities: artificial and natural phospholipid bilayers. Ann. N. Y. Acad. Sci, 1982, 38, 172-182.</p><p>Hashimoto K., Tatsumi N. Rapid isolation of human C- reactive protein and serum amyloid P component. J. Immunol. Methods, 1989, 125, 295-296.</p><p>Macintyre S.S. C-reactive protein. Methods Enzymol., 1988, 163, 383-399.</p><p>Potempa L.A., Maldonado B.A., Laurent P. Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium. Mol. Immunol, 1983, 20, 1165-1175.</p><p>Grabar P., Williams C.A. Some considerations of the problem of auto-antibody formation. Tex.Rep. Biol. Med., 1965, 23, 278-284.</p><p>Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 1970, 227. 680-685.</p><p>Nakagomi A., Freedman S.B., Geczy C.L. Interferon- gamma and lipopolysaccharide potentiate monocyte tissue factor induction by C-reactive protein: relationship with age, sex, and hormone replacement treatment. Circulation, 2000, 101, 1785-1791.</p><p>Haverkate F., Thompson S.G., Руке S.D. et al. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet. 1997, 349,462-466.</p><p>Yudkin J.S., Stehouwer C.D., Emeis J.J. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler. Thromb. Vase. Biol., 1999, 19, 972-978.</p></div><br /><div><p>Полевщиков А.В., Назаров П.Г. Роль С-реактивного белка и сывороточного амилоидного протеина А в иммунорегуляции. Иммунология, 1993, 4, 6-10.</p><p>Pepys М.В,Baltz M.L. Acute phase proteins with special reference to C-reactive protein and related proteins (pen- taxins) and seruni amyloid A protein. Adv. Immunol., 1983, 34, 141-212.</p><p>Borque L., Bellod L., Rus A. et al. Development and validation of an automated and ultrasensitive immunoturbidi- metric assay for C-reactive protein. Clin. Chem., 2000,46, 1839-1842.</p><p>Hutchinson W., Koenig W., Frohlich M. Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population. Clin. Chem., 2000. 46, 934-938.</p><p>Macy E.M., Hayes T.E., Tracy R.P. Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications.Clin. Chem., 1997,43, 52-58.</p><p>Macintyre S., Samols D., Dailey P.et al. Two car- boxylesterases bind C-reactive protein within the endoplasmic reticulum and regulate its secretion during the acute phase response.J. Biol. Chem., 1994, 269, 24496-24503.</p><p>Peltoia H., Rasanen J.A. C-reactive protein in rapid differentiation of acute epiglottitis from spasmodic croup and acute laryngotracheitis: a preliminary report. J. Pediatr., 1983, 102, 713-715.</p><p>Peltoia H„ Holmberg C. Rapidity of C-reactive protein in detecting potential septicemia. Pediatr. Infect. Dis., 1983,2. 374-376.</p><p>Maseri A. Inflammation, atherosclerosis, and ischemic events - exploring the hidden side of the moon. N.Engl. J. Med., 1997, 336. 1014-1016.</p><p>Peltoia H., Vahvanen V., Alto K. Fever, C-reactive protein, and erythrocyte sedimentation rate in monitoring recovery from septic arthritis: a preliminary study. J. Pediatr. Orthop., 1984, 4, 170-174.</p><p>Sharif М, Shepstone L., Elson C.J. et al. Increased serum C-reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee, Ann. Rheum. Dis., 2000, 59, 71-74.</p><p>Bataille R., Boccadoro М., Klein B. et al. C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. Blood, 1992, 80, 733-737.</p><p>Francis J.L. Laboratory investigation of hypercoagulability. Semin. Thromb. Hemost., 1998,24, 111-126.</p><p>Bick R.L. Coagulation abnormalities in malignancy: a review. Semin. Thromb. Hemost., 1992, 18, 353-372.</p><p>Zwaal R.F., Comfurius P., Bevers E.M. Lipid-protein interactions in blood coagulation. Biochim, Biophy. Acta, 1998, 1376, 433-453.</p><p>Oliveira E.B., Gotschlich E.C., Liu T.Y. Comparative studies on the binding properties of human and rabbit C-reactive proteins. J. Immunol., 1980, 124, 1396-1402.</p><p>Sui S., Sun Y., Mi L. Calcium-dependent binding of rabbit C-reactive protein to supported lipid monolayers containing exposed phosphorylcholine group. Biophys. J., 1999, 76, 333-341.</p><p>Pepys M.B., Rowe I.F., Baltz M. C-reactive protein: binding to lipids and lipoproteins. Int. Rev. Exp. Pathol., 1985, 27, 83-111.</p><p>de Beer F.C., Soutar A.K., Baltz M.L. Low density lipoprotein and very low density lipoprotein are selectively bound by aggregated C-reactive protein. J. Exp. Med., 1982, 156, 230-242.</p><p>Narkates A.J., Voianakis J.E. C-reactive protein binding specificities: artificial and natural phospholipid bilayers. Ann. N. Y. Acad. Sci, 1982, 38, 172-182.</p><p>Hashimoto K., Tatsumi N. Rapid isolation of human C- reactive protein and serum amyloid P component. J. Immunol. Methods, 1989, 125, 295-296.</p><p>Macintyre S.S. C-reactive protein. Methods Enzymol., 1988, 163, 383-399.</p><p>Potempa L.A., Maldonado B.A., Laurent P. Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium. Mol. Immunol, 1983, 20, 1165-1175.</p><p>Grabar P., Williams C.A. Some considerations of the problem of auto-antibody formation. Tex.Rep. Biol. Med., 1965, 23, 278-284.</p><p>Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 1970, 227. 680-685.</p><p>Nakagomi A., Freedman S.B., Geczy C.L. Interferon- gamma and lipopolysaccharide potentiate monocyte tissue factor induction by C-reactive protein: relationship with age, sex, and hormone replacement treatment. Circulation, 2000, 101, 1785-1791.</p><p>Haverkate F., Thompson S.G., Руке S.D. et al. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet. 1997, 349,462-466.</p><p>Yudkin J.S., Stehouwer C.D., Emeis J.J. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler. Thromb. Vase. Biol., 1999, 19, 972-978.</p></div><br />

The authors declare that there are no conflicts of interest present.