臨床検査54巻6号

2010年06月発行

今月の主題 注目されるサイトカイン 各論

注目されるケモカイン，ケモカイン受容体とその応用

著者： 松島綱治¹

所属機関： ¹東京大学大学院医学系研究科分子予防医学教室

ページ範囲：P.637 - P.643

　ケモカインは白血球遊走活性を有するタンパク質からなる生理活性物質であり，大きなファミリーを形成する．ケモカインは炎症・免疫反応を制御するのみならず癌に伴う血管新生・転移・増殖，HIV感染などにもかかわる．最近，AIDS治療薬としてのケモカイン受容体CCR5拮抗剤Maravirocと自家移植用幹細胞動員薬としてのCXCR4拮抗剤Plerixaforが臨床開発された．現在も多くの薬剤開発がケモカインシステムを標的として進行中である．

参考文献

1) Yoshimura T, Matsushima K, Tanaka S, et al：Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci USA　84：9233-9237, 1987

2) Matsushima K, Morishita K, Yoshimura T, et al：Molecular cloning of a human monocyte-derived neutrophil chemotactic factor(MDNCF)and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med　167：1883-1893, 1988

3) Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, et al：Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature　447：1116-1120, 2007

4) Sawanobori Y, Ueha S, Kurachi M, et al：Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood　111：5457-5466, 2008

5) Moore BB, Kolodsick JE, Thannickal VJ, et al：CCR2-mediated recruitment of fibrocytes to the alveolar space after fibrotic injury. Am J Pathol　166：675-684, 2005

6) Förster R, Mattis AE, Kremmer E, et al：A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell　87：1037-1047, 1996

7) Acosta-Rodriguez EV, Rivino L, Geginat J, et al：Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol　8：639-646, 2007

regulatory T cells to the paracortical areas of peripheral lymph nodes through high endothelial venules. J Leukoc Biol　2007；82：1230-1238.

9) Iwata M, Hirakiyama A, Eshima Y, et al：Retinoic acid imprints gut-homing specificity on T cells. Immunity　21：527-538, 2004

10) Sigmundsdottir H, Pan J, Debes GF, et al：DCs metabolize sunlight-induced vitamin D3 to ‘program' T cell attraction to the epidermal chemokine CCL27. Nat Immunol　8：285-293, 2007

11) Belperio JA, Keane MP, Arenberg DA, et al：CXC chemokines in angiogenesis. J Leukoc Biol　68：1-8, 2000

12) Sparmann A, Bar-Sagi D：Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell　6：447-458, 2004

13) Mizukami Y, Jo WS, Duerr EM, et al：Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells. Nat Med　11：992-997, 2005

14) Müller A, Homey B, Soto H, et al：Involvement of chemokine receptors in breast cancer metastasis. Nature　410：50-56, 2001

15) Miao Z, Luker KE, Summers BC, et al：CXCR7(RDC1)promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci USA　104：15735-15740, 2007

16) Ginestier C, Liu S, Diebel ME, et al：CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest　120：485-497, 2010

17) Feng Y, Broder CC, Kennedy PE, et al：HIV-1 entry cofactor：functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science　272：872-877, 1996

18) Dean M, Carrington M, Winkler C, et al：Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science　273：1856-1862, 1996

19) Yamamoto K, Utsunomiya A, Tobinai K, et al：Phase I Study of KW-0761, a Defucosylated Humanized Anti-CCR4 Antibody, in Relapsed Patients With Adult T-Cell Leukemia-Lymphoma and Peripheral T-Cell Lymphoma. J Clin Oncol 2010［Epub ahead of print］