臨床検査52巻13号

2008年12月発行

今月の主題 凝固制御 血液凝固系検査の新展開

単球由来マイクロパーティクル

著者： 野村昌作¹²

所属機関： ¹市立岸和田市民病院血液内科 ²関西医科大学

ページ範囲：P.1560 - P.1565

　活性化された細胞は微小な膜小胞体を遊離し，マイクロパーティクル(MP)と呼ばれている．MPは，血小板をはじめとして様々な細胞から生成されるが，単球に由来するMP(MDMP)は，その表面に強力な組織因子活性をもっている．MDMPは，組織因子に依存して凝固を促進する物質として働いているが，最近はそれ以外にもいくつかの機能を持っていることが判明している．なかでも重要なのが，物質の輸送作用と標的細胞に対する活性化作用である．MDMPは糖尿病，急性心筋梗塞，尿毒症，DICなどの血栓性疾患において検出されるが，最近は広範な臨床領域でMDMPの検出が報告されている．MDMPは，フローサイトメトリーによって比較的容易に検出でき，血管病変のメカニズムを考えるうえにおいて最も注目されている物質の一つでもある．

参考文献

1) George JN, Thoi LL, McManus LM, et al：Isolation of human platelet membrane microparticles from plasma and serum. Blood　60：834-840, 1982

2) Nomura S, Ozaki Y, Ikeda Y：Function and role of microparticles in various clinical settings. Thromb Res　123：8-23, 2008

3) Satta N, Toti F, Feugeas O, et al：Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide. J Immunol　153：3245-3255, 1994

4) Mesri M, Altieri DC：Endothelial cell activation by leukocyte microparticles. J Immunol　161：4382-4387, 1998

5) Omoto S, Nomura S, Shouzu A, et al：Detection of monocyte-derived microparticles in patients with Type II diabetes mellitus. Diabetologia　45：550-555, 2002

6) Matsumoto N, Nomura S, Kamihata H, et al：Increased level of oxidized LDL-dependent monocyte-derived microparticles in acute coronary syndrome. Thromb Haemost　91：146-154, 2004

7) Biró E, Sturk-Maquelin KN, Vogel GM, et al：Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost　1：2561-2568, 2003

8) Ogata N, Nomura S, Shouzu A, et al：Elevation of monocyte-derived microparticles in patients with diabetic retinopathy. Diabetes Res Clin Pract　73：241-248, 2006

9) Khan MM, Hattori T, Niewiarowski S, et al：Truncated and microparticle-free soluble tissue factor bound to peripheral monocytes preferentially activate factor VII. Thromb Haemost　95：462-468, 2006

10) Osterud B：The role of platelets in decrypting monocyte tissue factor. Semin Hematol　38：2-5, 2001

11) Nomura S, Kanazawa S, Fukuhara S：Effects of efonidipine on platelet and monocyte activation markers in hypertensive patients with and without type 2 diabetes mellitus. J Hum Hypertens　16：539-547, 2002

12) Nagahama M, Nomura S, Kanazawa S, et al：Significance of anti-oxidized LDL antibody and monocyte-derived microparticles in anti-phospholipid antibody syndrome. Autoimmunity　36：125-131, 2003

13) Martínez MC, Tesse A, Zobairi F, et al：Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol　288：H1004-H1009, 2005

14) Tushuizen ME, Nieuwland R, Scheffer PG, et al：Two consecutive high-fat meals affect endothelial-dependent vasodilation, oxidative stress and cellular microparticles in healthy men. J Thromb Haemost　4：1003-1010, 2006

15) Poitevin S, Cochery-Nouvellon E, Dupont A, et al：Monocyte IL-10 produced in response to lipopolysaccharide modulates thrombin generation by inhibiting tissue factor expression and release of active tissue factor-bound microparticles. Thromb Haemost　97：598-607, 2007

16) Hrachovinová I, Cambien B, Hafezi-Moghadam A, et al：Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nat Med　9：1020-1025, 2003

17) Gross PL, Furie BC, Merrill-Skoloff G, et al：Leukocyte-versus microparticle-mediated tissue factor transfer during arteriolar thrombus development. J Leukoc Biol　78：1318-1326, 2005

18) Falati S, Liu Q, Gross P, et al：Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med　197：1585-1598, 2003

19) Leroyer AS, Isobe H, Lesèche G, et al：Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol　49：772-777, 2007

20) André P, Hartwell D, Hrachovinová I, et al：Pro-coagulant state resulting from high levels of soluble P-selectin in blood. Proc Natl Acad Sci USA　97：13835-13840, 2000

21) Nomura S, Shouzu A, Omoto S, et al：Long-term treatment with nifedipine modulates procoagulant marker and C-C chemokine in hypertensive patients with type 2 diabetes mellitus. Thromb Res　115：277-285, 2005

22) Nomura S, Shouzu A, Omoto S, et al：Benidipine improves oxidized LDL-dependent monocyte and endothelial dysfunction in hypertensive patients with type 2 diabetes mellitus. J Hum Hypertens　19：551-557, 2005

23) Nomura S, Shouzu A, Omoto S, et al：Effect of valsartan on monocyte/endothelial cell activation markers and adiponectin in hypertensive patients with type 2 diabetes mellitus. Thromb Res　117：385-392, 2006

24) Kalinkovich A, Tavor S, Avigdor A, et al：Functional CXCR4-expressing microparticles and SDF-1 correlate with circulating acute myelogenous leukemia cells. Cancer Res　66：11013-11020, 2006

25) Tesselaar ME, Romijn FP, Van Der Linden IK, et al：Microparticle-associated tissue factor activity：a link between cancer and thrombosis? J Thromb Haemost　5：520-527, 2007

26) Lynch SF, Ludlam CA：Plasma microparticles and vascular disorders. Br J Haematol　137：36-48, 2007