進階搜尋


 
系統識別號 U0026-0812200910351650
論文名稱(中文) 單核球趨化蛋白-1刺激血管平滑肌細胞移行作用機制之探討
論文名稱(英文) The mechanisms of MCP-1-induced vascular smooth muscle cell migration
校院名稱 成功大學
系所名稱(中) 細胞生物及解剖學研究所
系所名稱(英) Institute of Cell Biology and Anatomy
學年度 91
學期 1
出版年 92
研究生(中文) 施俊名
研究生(英文) Jun-Ming Shih
學號 t9689106
學位類別 碩士
語文別 中文
論文頁數 78頁
口試委員 指導教授-江美治
口試委員-蔡美玲
召集委員-任卓穎
口試委員-何中良
中文關鍵字 單核球趨化蛋白-1  血管平滑肌細胞  移行作用 
英文關鍵字 smooth muscle cell  migration  MCP-1 
學科別分類
中文摘要   動脈硬化是一個形成原因極為複雜的血管疾病,是冠狀動脈硬化以及中風主要的致病機轉。在動脈硬化形成的過程中,平滑肌細胞從血管中層往內皮下間隙遷徙是一個造成動脈硬化斑重要的步驟。單核球趨化單白-1,是極有效的單核球趨化劑,被發現在血管受傷時會大量表現,因此被認為可以促進動脈硬化的發生。本實驗室之前的研究發現,GST-單核球趨化蛋白-1融合蛋白可以增加平滑肌細胞移行的活性,但是作用機制目前仍然不清楚。
  在本實驗中,我們使用大白鼠胚胎主動脈平滑肌細胞A7r5來探討市售單核球趨化蛋白-1對平滑肌細胞移行的影響。利用以塗上膠原蛋白type I或是fibronectin的濾膜,以modified Boyden chamber測定細胞移行作用,結果顯示單核球趨化蛋白-1明顯增加平滑肌細胞移行的能力,隨著單核球趨化蛋白-1濃度提高,平滑肌細胞的移行數目有逐漸增加的趨勢,在10-9M達到最大刺激效果。此外,棋盤分析法顯示,單核球趨化蛋白-1引起平滑肌細胞移行主要是透過趨化作用。另外,PI3K的抑制劑LY294002 (10μM)和wortmannin (50 和100nM)、Rho kinase的抑制劑 Y27632 (10μM)、 p38 MAPK抑制劑SB203580 (10μM)都能減少單核球趨化蛋白-1所引起的平滑肌細胞移行作用。有趣的是 ERK1/2活化抑制劑U0126 (10μM) 除了可以降低單核球趨化蛋白-1所引起的平滑肌細胞移行作用外,亦可減少移行的基礎值。西方墨點法的結果顯示,單核球趨化蛋白-1可以刺激ERK1/2磷酸化程度增加,並且可以被U0126和NADPH oxidase的抑制劑DPI所抑制,顯示氧活化中間產物可以引ERK1/2的活化。利用化學冷光法,我們發現,單核球趨化蛋白-1可以刺激平滑肌細胞產生氧活化中間產物,暗示單核球趨化蛋白-1確實會活化NADPH oxidase。此外,單核球趨化蛋白-1刺激氧活化中間產物的產生除了可以被DPI所抑制之外,U0126、PD98059 (50μM) 的抑制效果也很顯著。由這些結果顯示,單核球趨化蛋白-1是平滑肌細胞的趨化物質,且PI3K、 Rho kinase、 p38 MAPK、 ERK1/2 和 ROS都參與在單核球趨化蛋白-1所引發的平滑肌細胞移行作用中。此外,在單核球趨化蛋白-1的刺激之下,應有一個positve activation loop存在於ROS的產生與ERK1/2的活化之間
英文摘要   Atherosclerosis, a complex and multifactorial disease, is the underlying mechanism for vascular disorders including coronary artery disease and stroke. Vascular smooth muscle cells (VSMC) migration from media to subendothelial intima plays a major role in the lesion formation of atherosclerosis. Monocyte chemoattractant protein-1 (MCP-1), a potent monocyte attractant, is markedly upregulated during vascular injury and has been suggested to promote atherogenesis. Previous studies in our laboratory have found that recombinant glutathione S-transferase (GST)-fusion protein MCP-1 increased SMC migration activity. The mechanisms of this effect remain unclear, however.
  In the present study, we used rat embryonic aortic smooth muscle cell line A7r5 to investigate mechanisms mediating MCP-1-stimulated SMC migration activities. The migratory cell numbers were measured by modified Boyden chamber method using a polycarbonate membrane coated with type I collagen or fibronectin. The results showed that MCP-1 increased migration activity in a dose-dependent manner with 10-9M being maximally effective. In addition, checkerboard experiment showed that the response of A7r5 to MCP-1 is mainly chemotatic. Moreover, the phosphatidylinositol (PI) 3-kinase inhibitors LY294002 (10μM) and wortmannin (50nM and 100nM), Rho kinase inhibitor Y27632 (10μM) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (10μM) diminished MCP-1-induced SMC migration. Interestingly, the extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation inhibitor U0126 (10μM) abrogated both basal and MCP-1-induced migration. Immunoblottig results showed that MCP-1 increased ERK1/2 phosphorylation levels which were markedly decreased by U0126 and diphenyleneiodonium (DPI), an inhibitor for NADPH oxidase. This result indicated that reactive oxygen species (ROS) can lead to the activation of ERK1/2. Using chemiluminescence measurement, MCP-1 was found to increase intracellular production of ROS which was blocked by DPI, indicating that MCP-1 indeed activates NADPH oxidase. In addition to DPI, U0126 and PD98059 blocked MCP-1- dependent ROS generation. These results demonstrate that MCP-1 is a chemoattractant for SMC and that PI3K, Rho kinase, p38 MAPK, ERK1/2 and ROS are involved in MCP-1-stimulated migration. In addition, a postive activation loop appears to exist between ROS production and ERK1/2 activation during MCP-1 stimulation of SMC.
論文目次 中文摘要 I
Abstract III
目錄 V
緒論 1
藥品與儀器 13
材料與方法 19
  一、細胞培養 19
  二、平滑肌細胞的移行試驗 22
  三、細胞處理 24
  四、蛋白質定量 25
  五、蛋白質電泳分析(SDS-polyacrylamide gel electrophoresis analysis) 26
  六、西方墨點轉漬法 ( Western blot ) 28
  七、平滑肌細胞氧活化中間產物( ROS )的測定 32
  八、數據處理與統計分析 33
實驗結果 35
討論 43
參考文獻 53
圖68
參考文獻 Adams, D. H. and A. R. Lloyd (1997). "Chemokines: leucocyte recruitment and activation cytokines." Lancet 349(9050): 490-5.

Ai, S., M. Kuzuya, T. Koike, T. Asai, S. Kanda, K. Maeda, T. Shibata and A. Iguchi (2001). "Rho-Rho kinase is involved in smooth muscle cell migration through myosin light chain phosphorylation -dependent and independent pathways." Atherosclerosis 155(2): 321-7.

Alblas, J., L. Ulfman, P. Hordijk and L. Koenderman (2001). "Activation of Rhoa and ROCK are essential for detachment of migrating leukocytes." Mol Biol Cell 12(7): 2137-45.

Amano, M., K. Chihara, K. Kimura, Y. Fukata, N. Nakamura, Y. Matsuura and K. Kaibuchi (1997). "Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase." Science 275(5304): 1308-11.

Ashida, N., H. Arai, M. Yamasaki and T. Kita (2001). "Distinct signaling pathways for MCP-1-dependent integrin activation and chemotaxis." J Biol Chem 276(19): 16555-60.

Baggiolini, M., B. Dewald and B. Moser (1997). "Human chemokines: an update." Annu Rev Immunol 15: 675-705.

Barnes, M. J. and R. W. Farndale (1999). "Collagens and atherosclerosis." Exp Gerontol 34(4): 513-25.

Ben-Baruch, A., D. F. Michiel and J. J. Oppenheim (1995). "Signals and receptors involved in recruitment of inflammatory cells." J Biol Chem 270(20): 11703-6.

Cambien, B., M. Pomeranz, M. A. Millet, B. Rossi and A. Schmid-Alliana (2001). "Signal transduction involved in MCP-1-mediated monocytic transendothelial migration." Blood 97(2): 359-66.

Carey, D. J. (1991). "Control of growth and differentiation of vascular cells by extracellular matrix proteins." Annu Rev Physiol 53: 161-77.

Chamley, J. H., G. R. Campbell, J. D. McConnell and U. Groschel-Stewart (1977). "Comparison of vascular smooth muscle cells from adult human, monkey and rabbit in primary culture and in subculture." Cell Tissue Res 177(4): 503-22.

Chamley-Campbell, J. H., G. R. Campbell and R. Ross (1981). "Phenotype-dependent response of cultured aortic smooth muscle to serum mitogens." J Cell Biol 89(2): 379-83.

Chardin, P., P. Madaule and A. Tavitian (1988). "Coding sequence of human rho cDNAs clone 6 and clone 9." Nucleic Acids Res 16(6): 2717.

Chen, Y. L., Y. J. Chang and M. J. Jiang (1999). "Monocyte chemotactic protein-1 gene and protein expression in atherogenesis of hypercholesterolemic rabbits." Atherosclerosis 143(1): 115-23.

Chensue, S. W., K. S. Warmington, J. H. Ruth, P. S. Sanghi, P. Lincoln and S. L. Kunkel (1996). "Role of monocyte chemoattractant protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: relationship to local inflammation, Th cell expression, and IL-12 production." J Immunol 157(10): 4602-8.

Chung, C. Y., S. Funamoto and R. A. Firtel (2001). "Signaling pathways controlling cell polarity and chemotaxis." Trends Biochem Sci 26(9): 557-66.

Clowes, A. W. and M. M. Clowes (1986). "Kinetics of cellular proliferation after arterial injury. IV. Heparin inhibits rat smooth muscle mitogenesis and migration." Circ Res 58(6): 839-45.

Cushing, S. D., J. A. Berliner, A. J. Valente, M. C. Territo, M. Navab, F. Parhami, R. Gerrity, C. J. Schwartz and A. M. Fogelman (1990). "Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells." Proc Natl Acad Sci U S A 87(13): 5134-8.

Denes, L., A. Jednakovits, J. Hargitai, Z. Penzes, A. Balla, L. Talosi, P. Krajcsi and P. Csermely (2002). "Pharmacologically activated migration of aortic endothelial cells is mediated through p38 SAPK." Br J Pharmacol 136(4): 597-603.

Denger, S., L. Jahn, P. Wende, L. Watson, S. H. Gerber, W. Kubler and J. Kreuzer (1999). "Expression of monocyte chemoattractant protein-1 cDNA in vascular smooth muscle cells: induction of the synthetic phenotype: a possible clue to SMC differentiation in the process of atherogenesis." Atherosclerosis 144(1): 15-23.

Derijard, B., J. Raingeaud, T. Barrett, I. H. Wu, J. Han, R. J. Ulevitch and R. J. Davis (1995). "Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms." Science 267(5198): 682-5.

Edelman, E. R., M. A. Nugent, L. T. Smith and M. J. Karnovsky (1992). "Basic fibroblast growth factor enhances the coupling of intimal hyperplasia and proliferation of vasa vasorum in injured rat arteries." J Clin Invest 89(2): 465-73.

Egashira, K., Q. Zhao, C. Kataoka, K. Ohtani, M. Usui, I. F. Charo, K. Nishida, S. Inoue, M. Katoh, T. Ichiki and A. Takeshita (2002). "Importance of monocyte chemoattractant protein-1 pathway in neointimal hyperplasia after periarterial injury in mice and monkeys." Circ Res 90(11): 1167-72.

Fager, G., G. Camejo and G. Bondjers (1992). "Heparin-like glycosaminoglycans influence growth and phenotype of human arterial smooth muscle cells in vitro. I. Evidence for reversible binding and inactivation of the platelet-derived growth factor by heparin." In Vitro Cell Dev Biol 28A(3 Pt 1): 168-75.

Falk, W., R. H. Goodwin, Jr. and E. J. Leonard (1980). "A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration." J Immunol Methods 33(3): 239-47.

Finkel, T. (1998). "Oxygen radicals and signaling." Curr Opin Cell Biol 10(2): 248-53.

Frostegard, J., Y. H. Huang, J. Ronnelid and L. Schafer-Elinder (1997). "Platelet-activating factor and oxidized LDL induce immune activation by a common mechanism." Arterioscler Thromb Vasc Biol 17(5): 963-8.

Fuentes, M. E., S. K. Durham, M. R. Swerdel, A. C. Lewin, D. S. Barton, J. R. Megill, R. Bravo and S. A. Lira (1995). "Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1." J Immunol 155(12): 5769-76.

Furukawa, Y., A. Matsumori, N. Ohashi, T. Shioi, K. Ono, A. Harada, K. Matsushima and S. Sasayama (1999). "Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries." Circ Res 84(3): 306-14.

Goncharova, E. A., A. V. Vorotnikov, E. O. Gracheva, W. C. Albert, R. A. Panettieri, Jr., V. V. Stepanova and V. A. Tkachuk (2002). "Activation of p38 MAP-kinase and caldesmon phosphorylation are essential for urokinase-induced human smooth muscle cell migration." Biol Chem 383(1): 115-26.

Granfeldt, D., M. Samuelsson and A. Karlsson (2002). "Capacitative Ca2+ influx and activation of the neutrophil respiratory burst. Different regulation of plasma membrane- and granule-localized NADPH-oxidase." J Leukoc Biol 71(4): 611-7.

Grewal, I. S., B. J. Rutledge, J. A. Fiorillo, L. Gu, R. P. Gladue, R. A. Flavell and B. J. Rollins (1997). "Transgenic monocyte chemoattractant protein-1 (MCP-1) in pancreatic islets produces monocyte-rich insulitis without diabetes: abrogation by a second transgene expressing systemic MCP-1." J Immunol 159(1): 401-8.

Griendling, K. K., D. Sorescu, B. Lassegue and M. Ushio-Fukai (2000). "Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology." Arterioscler Thromb Vasc Biol 20(10): 2175-83.

Griendling, K. K., D. Sorescu and M. Ushio-Fukai (2000). "NAD(P)H oxidase: role in cardiovascular biology and disease." Circ Res 86(5): 494-501.

Gunn, M. D., N. A. Nelken, X. Liao and L. T. Williams (1997). "Monocyte chemoattractant protein-1 is sufficient for the chemotaxis of monocytes and lymphocytes in transgenic mice but requires an additional stimulus for inflammatory activation." J Immunol 158(1): 376-83.

Hall, A. (1998). "Rho GTPases and the actin cytoskeleton." Science 279(5350): 509-14.

Han, J., J. D. Lee, L. Bibbs and R. J. Ulevitch (1994). "A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells." Science 265(5173): 808-11.

Hayes, I. M., N. J. Jordan, S. Towers, G. Smith, J. R. Paterson, J. J. Earnshaw, A. G. Roach, J. Westwick and R. J. Williams (1998). "Human vascular smooth muscle cells express receptors for CC chemokines." Arterioscler Thromb Vasc Biol 18(3): 397-403.

Hedges, J. C., M. A. Dechert, I. A. Yamboliev, J. L. Martin, E. Hickey, L. A. Weber and W. T. Gerthoffer (1999). "A role for p38(MAPK)/HSP27 pathway in smooth muscle cell migration." J Biol Chem 274(34): 24211-9.

Hirsch, E., V. L. Katanaev, C. Garlanda, O. Azzolino, L. Pirola, L. Silengo, S. Sozzani, A. Mantovani, F. Altruda and M. P. Wymann (2000). "Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation." Science 287(5455): 1049-53.

Hishikawa, K., T. Nakaki, T. Marumo, M. Hayashi, H. Suzuki, R. Kato and T. Saruta (1994). "Pressure promotes DNA synthesis in rat cultured vascular smooth muscle cells." J Clin Invest 93(5): 1975-80.

Imai, Y. and D. R. Clemmons (1999). "Roles of phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in stimulation of vascular smooth muscle cell migration and deoxyriboncleic acid synthesis by insulin-like growth factor-I." Endocrinology 140(9): 4228-35.

Irani, K. (2000). "Oxidant signaling in vascular cell growth, death, and survival : a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling." Circ Res 87(3): 179-83.

Jin, T., N. Zhang, Y. Long, C. A. Parent and P. N. Devreotes (2000). "Localization of the G protein betagamma complex in living cells during chemotaxis." Science 287(5455): 1034-6.

Jones, R. D., J. T. Hancock and A. H. Morice (2000). "NADPH oxidase: a universal oxygen sensor?" Free Radic Biol Med 29(5): 416-24.

Jordan, N. J., M. L. Watson, R. J. Williams, A. G. Roach, T. Yoshimura and J. Westwick (1997). "Chemokine production by human vascular smooth muscle cells: modulation by IL-13." Br J Pharmacol 122(4): 749-57.

Keiji Kito and Ken-ichiNishida (2002). "Nonrequirement of continuous stimulation with MCP-1 for cell migration and determination of directional migration by initial stimulation with chemokine." Exp Cell Research 281, 157-166

Koch, A. E., S. L. Kunkel, L. A. Harlow, B. Johnson, H. L. Evanoff, G. K. Haines, M. D. Burdick, R. M. Pope and R. M. Strieter (1992). "Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis." J Clin Invest 90(3): 772-9.

Krymskaya, V. P., R. B. Penn, M. J. Orsini, P. H. Scott, R. J. Plevin, T. R. Walker, A. J. Eszterhas, Y. Amrani, E. R. Chilvers and R. A. Panettieri, Jr. (1999). "Phosphatidylinositol 3-kinase mediates mitogen-induced human airway smooth muscle cell proliferation." Am J Physiol 277(1 Pt 1): L65-78.

Laudanna, C., J. J. Campbell and E. C. Butcher (1996). "Role of Rho in chemoattractant-activated leukocyte adhesion through integrins." Science 271(5251): 981-3.

Leevers, S. J., B. Vanhaesebroeck and M. D. Waterfield (1999). "Signalling through phosphoinositide 3-kinases: the lipids take centre stage." Curr Opin Cell Biol 11(2): 219-25.

Leeuwen RTJ. (1996) Extracellular proteolysis and the migrating vascular smooth muscle cell. Fibrinolysis 10:59-74

Leonard, E. J. and T. Yoshimura (1990). "Human monocyte chemoattractant protein-1 (MCP-1)." Immunol Today 11(3): 97-101.

Li, W., C. Nadelman, G. Henry, J. Fan, M. Muellenhoff, E. Medina, N. S. Gratch, M. Chen, J. Han and D. Woodley (2001). "The p38-MAPK/SAPK pathway is required for human keratinocyte migration on dermal collagen." J Invest Dermatol 117(6): 1601-11.

Li, Z., H. Jiang, W. Xie, Z. Zhang, A. V. Smrcka and D. Wu (2000). "Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant- mediated signal transduction." Science 287(5455): 1046-9.

Lin, A., A. Minden, H. Martinetto, F. X. Claret, C. Lange-Carter, F. Mercurio, G. L. Johnson and M. Karin (1995). "Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2." Science 268(5208): 286-90.

Lopez-Ilasaca, M. (1998). "Signaling from G-protein-coupled receptors to mitogen-activated protein (MAP)-kinase cascades." Biochem Pharmacol 56(3): 269-77.

Luscher, T. F. (1994). "Endothelium in the control of vascular tone and growth: role of local mediators and mechanical forces." Blood Press Suppl 1: 18-22.

Maesaki, R., K. Ihara, T. Shimizu, S. Kuroda, K. Kaibuchi and T. Hakoshima (1999). "The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1." Mol Cell 4(5): 793-803.

Marumo, T., V. B. Schini-Kerth, B. Fisslthaler and R. Busse (1997). "Platelet-derived growth factor-stimulated superoxide anion production modulates activation of transcription factor NF-kappaB and expression of monocyte chemoattractant protein 1 in human aortic smooth muscle cells." Circulation 96(7): 2361-7.

Mitchell, R., D. McCulloch, E. Lutz, M. Johnson, C. MacKenzie, M. Fennell, G. Fink, W. Zhou and S. C. Sealfon (1998). "Rhodopsin-family receptors associate with small G proteins to activate phospholipase D." Nature 392(6674): 411-4.

Nakayama, K. and Y. Tanaka (1993). "Stretch-induced contraction and Ca2+ mobilization in vascular smooth muscle." Biol Signals 2(5): 241-52.

Narumiya, S. and N. Morii (1993). "rho gene products, botulinum C3 exoenzyme and cell adhesion." Cell Signal 5(1): 9-19.

Navab, M., S. S. Imes, S. Y. Hama, G. P. Hough, L. A. Ross, R. W. Bork, A. J. Valente, J. A. Berliner, D. C. Drinkwater, H. Laks and et al. (1991). "Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein." J Clin Invest 88(6): 2039-46.

Nguyen, D. H., A. D. Catling, D. J. Webb, M. Sankovic, L. A. Walker, A. V. Somlyo, M. J. Weber and S. L. Gonias (1999). "Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner." J Cell Biol 146(1): 149-64.

Nishio, E. and Y. Watanabe (1997). "The involvement of reactive oxygen species and arachidonic acid in alpha 1-adrenoceptor-induced smooth muscle cell proliferation and migration." Br J Pharmacol 121(4): 665-70.

Palmberg, L., H. E. Claesson and J. Thyberg (1989). "Effects of leukotrienes on phenotypic properties and growth of arterial smooth muscle cells in primary culture." J Cell Sci 93 ( Pt 3): 403-8.

Patterson, C., J. Ruef, N. R. Madamanchi, P. Barry-Lane, Z. Hu, C. Horaist, C. A. Ballinger, A. R. Brasier, C. Bode and M. S. Runge (1999). "Stimulation of a vascular smooth muscle cell NAD(P)H oxidase by thrombin. Evidence that p47(phox) may participate in forming this oxidase in vitro and in vivo." J Biol Chem 274(28): 19814-22.

Piotrowicz, R. S. and E. G. Levin (1997). "Basolateral membrane-associated 27-kDa heat shock protein and microfilament polymerization." J Biol Chem 272(41): 25920-7.

Plow, E. F., T. A. Haas, L. Zhang, J. Loftus and J. W. Smith (2000). "Ligand binding to integrins." J Biol Chem 275(29): 21785-8.

Prescott, S. M., T. M. McIntyre, G. A. Zimmerman and D. M. Stafforini (1996). "Inflammation as an early component of atherosclerosis and vascular damage--a role for P-selectin and platelet-activating factor." Jpn Circ J 60(3): 137-41.

Raines, E. W. (2000). "The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease." Int J Exp Pathol 81(3): 173-82.

Ren, X. D., W. B. Kiosses and M. A. Schwartz (1999). "Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton." Embo J 18(3): 578-85.

Rollins, B. J., T. Yoshimura, E. J. Leonard and J. S. Pober (1990). "Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE." Am J Pathol 136(6): 1229-33.

Roque, M., W. J. Kim, M. Gazdoin, A. Malik, E. D. Reis, J. T. Fallon, J. J. Badimon, I. F. Charo and M. B. Taubman (2002). "CCR2 deficiency decreases intimal hyperplasia after arterial injury." Arterioscler Thromb Vasc Biol 22(4): 554-9.

Rosenfeld, M. E. (1991). "Oxidized LDL affects multiple atherogenic cellular responses." Circulation 83(6): 2137-40.

Ross, R. (1993). "The pathogenesis of atherosclerosis: a perspective for the 1990s." Nature 362(6423): 801-9.

Ross, R. (1999). "Atherosclerosis--an inflammatory disease." N Engl J Med 340(2): 115-26.

Salcedo, R., M. L. Ponce, H. A. Young, K. Wasserman, J. M. Ward, H. K. Kleinman, J. J. Oppenheim and W. J. Murphy (2000). "Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression." Blood 96(1): 34-40.

Sasaki, T., J. Irie-Sasaki, R. G. Jones, A. J. Oliveira-dos-Santos, W. L. Stanford, B. Bolon, A. Wakeham, A. Itie, D. Bouchard, I. Kozieradzki, N. Joza, T. W. Mak, P. S. Ohashi, A. Suzuki and J. M. Penninger (2000). "Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration." Science 287(5455): 1040-6.

Schecter, A. D., B. J. Rollins, Y. J. Zhang, I. F. Charo, J. T. Fallon, M. Rossikhina, P. L. Giesen, Y. Nemerson and M. B. Taubman (1997). "Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells." J Biol Chem 272(45): 28568-73.

Schwartz, S. M., G. R. Campbell and J. H. Campbell (1986). "Replication of smooth muscle cells in vascular disease." Circ Res 58(4): 427-44.

Seasholtz, T. M., M. Majumdar and J. H. Brown (1999). "Rho as a mediator of G protein-coupled receptor signaling." Mol Pharmacol 55(6): 949-56.

Seasholtz, T. M., M. Majumdar, D. D. Kaplan and J. H. Brown (1999). "Rho and Rho kinase mediate thrombin-stimulated vascular smooth muscle cell DNA synthesis and migration." Circ Res 84(10): 1186-93.

Servant, G., O. D. Weiner, P. Herzmark, T. Balla, J. W. Sedat and H. R. Bourne (2000). "Polarization of chemoattractant receptor signaling during neutrophil chemotaxis." Science 287(5455): 1037-40.

Skinner, M. P., E. W. Raines and R. Ross (1994). "Dynamic expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors by human vascular smooth muscle cells. Alpha 2 beta 1 integrin is required for chemotaxis across type I collagen-coated membranes." Am J Pathol 145(5): 1070-81.

Slepian, M. J., S. P. Massia, B. Dehdashti, A. Fritz and L. Whitesell (1998). "Beta3-integrins rather than beta1-integrins dominate integrin-matrix interactions involved in postinjury smooth muscle cell migration." Circulation 97(18): 1818-27.

Sorescu, D., K. Szocs and K. K. Griendling (2001). "NAD(P)H oxidases and their relevance to atherosclerosis." Trends Cardiovasc Med 11(3-4): 124-31.

Streblow, D. N., C. Soderberg-Naucler, J. Vieira, P. Smith, E. Wakabayashi, F. Ruchti, K. Mattison, Y. Altschuler and J. A. Nelson (1999). "The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration." Cell 99(5): 511-20.

Strieter, R. M., R. Wiggins, S. H. Phan, B. L. Wharram, H. J. Showell, D. G. Remick, S. W. Chensue and S. L. Kunkel (1989). "Monocyte chemotactic protein gene expression by cytokine-treated human fibroblasts and endothelial cells." Biochem Biophys Res Commun 162(2): 694-700.

Sundaresan, M., Z. X. Yu, V. J. Ferrans, K. Irani and T. Finkel (1995). "Requirement for generation of H2O2 for platelet-derived growth factor signal transduction." Science 270(5234): 296-9.

Suzuki, Y. J., H. J. Forman and A. Sevanian (1997). "Oxidants as stimulators of signal transduction." Free Radic Biol Med 22(1-2): 269-85.

Tamura, M., T. Kai, S. Tsunawaki, J. D. Lambeth and K. Kameda (2000). "Direct interaction of actin with p47(phox) of neutrophil NADPH oxidase." Biochem Biophys Res Commun 276(3): 1186-90.

Tangkijvanich, P., C. Santiskulvong, A. C. Melton, E. Rozengurt and H. F. Yee, Jr. (2002). "p38 MAP kinase mediates platelet-derived growth factor-stimulated migration of hepatic myofibroblasts." J Cell Physiol 191(3): 351-61.

Terkeltaub, R., W. A. Boisvert and L. K. Curtiss (1998). "Chemokines and atherosclerosis." Curr Opin Lipidol 9(5): 397-405.

Thyberg, J., U. Hedin, M. Sjolund, L. Palmberg and B. A. Bottger (1990). "Regulation of differentiated properties and proliferation of arterial smooth muscle cells." Arteriosclerosis 10(6): 966-90.

Turner, S. J., J. Domin, M. D. Waterfield, S. G. Ward and J. Westwick (1998). "The CC chemokine monocyte chemotactic peptide-1 activates both the class I p85/p110 phosphatidylinositol 3-kinase and the class II PI3K-C2alpha." J Biol Chem 273(40): 25987-95.

Ushio-Fukai, M., R. W. Alexander, M. Akers and K. K. Griendling (1998). "p38 Mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin II. Role in vascular smooth muscle cell hypertrophy." J Biol Chem 273(24): 15022-9.

Valente, A. J., D. T. Graves, C. E. Vialle-Valentin, R. Delgado and C. J. Schwartz (1988). "Purification of a monocyte chemotactic factor secreted by nonhuman primate vascular cells in culture." Biochemistry 27(11): 4162-8.

Van Aelst, L. and C. D'Souza-Schorey (1997). "Rho GTPases and signaling networks." Genes Dev 11(18): 2295-322.

Van der Goes, A., D. Wouters, S. M. Van Der Pol, R. Huizinga, E. Ronken, P. Adamson, J. Greenwood, C. D. Dijkstra and H. E. De Vries (2001). "Reactive oxygen species enhance the migration of monocytes across the blood-brain barrier in vitro." Faseb J 15(10): 1852-4.

Vanderkerken, K., I. V. Broek, D. L. Eizirik, V. E. Van, K. Asosingh, R. I. Van and C. B. Van (2002). "Monocyte chemoattractant protein-1 (MCP-1), secreted by bone marrow endothelial cells, induces chemoattraction of 5T multiple myeloma cells." Clin Exp Metastasis 19(1): 87-90.

Viedt, C., J. Vogel, T. Athanasiou, W. Shen, S. R. Orth, W. Kubler and J. Kreuzer (2002). "Monocyte chemoattractant protein-1 induces proliferation and interleukin-6 production in human smooth muscle cells by differential activation of nuclear factor-kappaB and activator protein-1." Arterioscler Thromb Vasc Biol 22(6): 914-20.

Volk, T., M. Hensel, H. Schuster and W. J. Kox (2000). "Secretion of MCP-1 and IL-6 by cytokine stimulated production of reactive oxygen species in endothelial cells." Mol Cell Biochem 206(1-2): 105-12.

Wang, J. M., A. Sica, G. Peri, S. Walter, I. M. Padura, P. Libby, M. Ceska, I. Lindley, F. Colotta and A. Mantovani (1991). "Expression of monocyte chemotactic protein and interleukin-8 by cytokine-activated human vascular smooth muscle cells." Arterioscler Thromb 11(5): 1166-74.

Wang, Z., M. R. Castresana and W. H. Newman (2001). "Reactive oxygen and NF-kappaB in VEGF-induced migration of human vascular smooth muscle cells." Biochem Biophys Res Commun 285(3): 669-74.

Wedgwood, S., R. W. Dettman and S. M. Black (2001). "ET-1 stimulates pulmonary arterial smooth muscle cell proliferation via induction of reactive oxygen species." Am J Physiol Lung Cell Mol Physiol 281(5): L1058-67.

Wempe, F., V. Lindner and H. G. Augustin (1997). "Basic fibroblast growth factor (bFGF) regulates the expression of the CC chemokine monocyte chemoattractant protein-1 (MCP-1) in autocrine-activated endothelial cells." Arterioscler Thromb Vasc Biol 17(11): 2471-8.

Willis, A. I., S. Fuse, X. J. Wang, E. Chen, G. P. Tuszynski, B. E. Sumpio and V. Gahtan (2000). "Inhibition of phosphatidylinositol 3-kinase and protein kinase C attenuates extracellular matrix protein-induced vascular smooth muscle cell chemotaxis." J Vasc Surg 31(6): 1160-7.

Yamamoto, M., K. Yamamoto and T. Noumura (1993). "Type I collagen promotes modulation of cultured rabbit arterial smooth muscle cells from a contractile to a synthetic phenotype." Exp Cell Res 204(1): 121-9.

Yamboliev, I. A., J. Chen and W. T. Gerthoffer (2001). "PI 3-kinases and Src kinases regulate spreading and migration of cultured VSMCs." Am J Physiol Cell Physiol 281(2): C709-18.

Yamboliev, I. A. and W. T. Gerthoffer (2001). "Modulatory role of ERK MAPK-caldesmon pathway in PDGF-stimulated migration of cultured pulmonary artery SMCs." Am J Physiol Cell Physiol 280(6): C1680-8.

Yen, H., Y. Zhang, S. Penfold and B. J. Rollins (1997). "MCP-1-mediated chemotaxis requires activation of non-overlapping signal transduction pathways." J Leukoc Biol 61(4): 529-32.

Yla-Herttuala, S., B. A. Lipton, M. E. Rosenfeld, T. Sarkioja, T. Yoshimura, E. J. Leonard, J. L. Witztum and D. Steinberg (1991). "Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions." Proc Natl Acad Sci U S A 88(12): 5252-6.

Yoshimura, T., E. A. Robinson, S. Tanaka, E. Appella, J. Kuratsu and E. J. Leonard (1989). "Purification and amino acid analysis of two human glioma-derived monocyte chemoattractants." J Exp Med 169(4): 1449-59.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2003-02-11起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2003-02-11起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw