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研究生:劉思顏
研究生(外文):Liu, Si-Yen
論文名稱:氧化還原調節作用在very late antigen-4 integrin所媒介的白血球活化與toluene diisocyanate所誘發的肺部發炎反應中所扮演的角色
論文名稱(外文):The role of redox modulation in very late antigen-4 integrin mediated leukocyte activation and toluene diisocyanate induced airway inflammation
指導教授:謝奇璋謝奇璋引用關係
指導教授(外文):Shieh, Chi-Chang
口試委員:莊偉哲張明熙葉才明戴任恭洪志興
口試日期:2010-06-21
學位類別:博士
校院名稱:國立成功大學
系所名稱:基礎醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:英文
論文頁數:114
中文關鍵詞:白血球運行細胞黏著分子肺部發炎菸醯胺腺嘌呤二核酸磷酸氧化酶氧自由基
外文關鍵詞:leukocytes traffickingredox modulationintegrinreactive oxygen speciesNADPH oxidaseairway inflammation
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在發炎反應的過程中,血流內的白血球通过多重且具有選擇性之細胞間的黏附作用而進行移行,此項複雜且多變程序對於特異性的招募白血球抵達發炎組織是相當重要的。如同其他類型免疫反應,關於過敏炎症,例如氣喘,的起始與發展中,白血球是如何被活化進而聚集在呼吸道而造成發炎是項有趣的研究課題。我們推測微環境中的氧自由基也許透過氧化還原作用來調控免疫反應並且使用體外與活體內的系統來釐清白血球所產生的氧自由基是否在白血球活化作用和過敏疾病中扮演一個重要角色。白血球integrin的活化對於細胞運轉至組織是重要的。
我們先前的研究顯示, very late antigen-4 integrin (VLA-4 integrin)與vascular cell adhesion molecule-1 (VCAM-1)之間的接合反應可受氧自由基的調整。 本篇論文中,我們探討了氧化還原的特質在VLA-4分子活化後的alpha 4 chain上曝露出的半胱氨基酸的影響性。結果顯示,低濃度的過氧化氫處理下(5-10M) 能夠增強 VLA-4 integrin 與 VCAM-1 的結合作用,與細胞黏著作用,此外也能增加活化態的VLA-4 integrin 的表現。反之高濃度的過氧化氫的處理下則不然。 低濃度的過氧化氫導致VLA-4 integrin發生S-glutathionylation作用,VLA-4integrin與配體的結合能力可受氧化還原反應所調節並且也需要外部傳訊系統和細胞骨架重整所參與。這些研究結果表明VLA-4活化須有氧化還原作用的參與,這個現象在指揮白血球進入發炎組織中也許扮演一個關鍵性角色。我們利用了小鼠肺部發炎模式來探討白血球被產生的氧化劑呼吸道發炎中所扮演的角色,我們利用了一種會導致職業性氣喘的低分子量化合物,甲苯二異氰酸鹽,來誘發小鼠肺部發炎。菸醯胺腺嘌呤二核酸磷酸氧化酶在白血球中是大量表現的酵素,在組織發炎時是重要的氧自由基來源。野生型B6老鼠和Ncf1-/-老鼠由鼻腔注入甲苯二異氰酸鹽以進行致敏化並且藉由吸入霧化的甲苯二異氰酸鹽以進行刺激。結果顯示在Ncf1-/-老鼠的肺組織和肺泡灌洗液體中的白血球浸潤明顯減少了。在Ncf1-/-老鼠中對於乙醯甲胆鹼刺激後的呼吸道收縮反應也降低至基礎線水平值。此外在Ncf1-/-老鼠組織中,甲苯二異氰酸鹽所誘發表現的細胞激素與氧化還原敏感型的核蛋白明顯減少了。我們的研究結果推測白血球菸醯胺腺嘌呤二核酸磷酸氧化酶在甲苯二異氰酸鹽導致的肺部發炎症狀中是一個必要的調節者。
The trafficking of leukocytes from the blood into peripheral tissues through a multiple-step intercellular adhesion process is essential for selective recruitment of leukocytes to the inflammation sites. Like other immune reactions, a central question regarding the initiation and progression of allergic inflammation which leads to diseases like asthma is how cells responsible for stimulations are selectively recruited to the airway. We suggest that reactive oxygen species in the tissue microenvironments may participate in the regulation of immune responses by redox modulation and use in vitro and in vivo systems to address whether leukocyte-produced reactive oxygen species play an important role in leukocytes activation and allergic disease. Activation of leukocyte integrin is important for selective recruitment of cells to tissues. Our previous studies showed that the binding between the integrin very late antigen-4 (VLA-4) and vascular cell adhesion molecule-1 (VCAM-1) is modulated by reactive oxygen species. Here, we investigated the molecular nature of redox modulation on the activation states of VLA-4 induced exposure of sulfhydryl groups on the alpha 4 peptide. Low concentrations of exogenous hydrogen peroxide (5-10M) enhanced the ligand binding ability of VLA-4 to VCAM-1 and cell rolling on VCAM-1, while higher concentrations of hydrogen peroxide (100M) inhibited the binding ability. Low concentration hydrogen peroxide induced the S-glutathionylation on VLA-4 and the VLA-4 ligand binding activity modulated by redox modulation and required outside-in signaling and cytoskeleton rearrangement. These findings indicated that ligand binding of VLA-4 involves redox modulations which may play a pivotal role in regulating the activation states of VLA-4 in inflammatory tissues and hence direct leukocyte trafficking. To address the role of leukocyte-produced oxidants in airway inflammation, toluene diisocyanate, a low molecular weight compound noted for inducing occupational asthma, was used to induce airway inflammation in a mouse model.  NADPH oxidase highly expressed in leukocytes has been known to be critical in reactive oxygen species production during tissue inflammation. Wild type B6 mice and NADPH oxidase deficiency (Ncf1-/-) mice were sensitized by intranasal sensitization and challenged by inhalation with toluene diisocyanate. Cell infiltration in lung tissue and leukocytes in bronchoalveolar lavage markedly decreased in the Ncf1-/- animals. Airway reactivity to methacholine challenge also was reduced to baseline level in Ncf1-/- mice. Toluene diisocyanate-induced inflammatory cytokines expression and redox-sensitvie nuclear factor activation in the lung tissue markedly decreased in NADPH oxidase deficient mice. Our findings suggest that leukocyte NADPH oxidase may be an essential regulator in toluene diisocyanate-induced airway inflammation.
Abstract in Chinese…………………………………………………………………...3
Abstract in English..………………………………………………………………….5
Abbreviations………………………………………………………………………...14
Chapter 1 Introduction……………………………………………………………...16
1.1 Redox biology………………………………………………………………..17
1.2 Cell adhesion molecules and cellular immune response……………………..18
1.3 The interactions between VLA-4 and VCAM-1…………………………….20
1.4 Leukocyte NADPH oxidase system……………………………………….20
1.5 Redox modulation and Integrin activation…………………………………...22
1.6 Oxidative stress, redox modulation and pulmonary disease…………………23
Chapter 2 Materials and Methods…………………………………………26
2.1 Cells, reagents and antibodies………………………………………………..27
2.2 Cell adhesion assay…………………………………………………………..27
2.3 Cell surface labeling, immuno-precipitation and western blotting…………..28
2.4 Fluorescein isothiocyante (FITC) labeled VCAM-1-Fc binding assay……...29
2.5 Cell rolling assay……………………………………………………………..30
2.6 Transfection of FAK siRNA………………………………………………....31
2.7 Animal and Toluene diisocyanate or ovalbumin exposure.…………………..31
2.8 Sampling and cellular analysis of bronchoalveolar lavage fluid….………….32
2.9 Lung tissue collection, staining and histology examination….……………....33
2.10 Measurement of airway responsiveness…...………………………………..33
2.11 Examination of total sulfhydryl level, protein glutathionylaiton/carbonylation and reactive oxygen species generation in lung……………34
2.12 Preparation of toluene diisocyanate- bovine serum albumin conjugate and antibody detection…35
2.13 Preparation of nuclear extracts……………………………………………...36
2.14 Measurement of cytokines…………………………………………………..36
2.15 Cell depletion experiment…………...……………………………………....37
2.16 Statistical analyses…………………………………………………………..37
Chapter 3 Results…………………………………………………………38
3.1 Sulfhydryl blockers inhibit the cell adhesion of HL-60 clone 15 cells to VCAM-1 and suppress the ligand-induced activation of VLA-4…………….39
3.2 The binding of VLA-4 to VCAM-1 involves changes in exposed sulfhydryl group on VLA-4 α4 chain……………………………………………………40
3.3 Redox modification of VLA-4 by exogenous ROS modulates its intrinsic ligand binding activity……………………………………………………..41
3.4 Hydrogen peroxide regulates the HL-60 clone 15 cellular binding and cell rolling mediated by VLA-4………………………………………………….42
3.5 Cytoskeleton reorganization and cellular signaling are involved in redox modulation of VLA-4 integrin ligand binding…………………………...….43
3.6 TDI exposure and leukocyte NADPH oxidase activity induce oxidant stress in the lung……44
3.7 TDI exposure induces airway hyperresponsiveness in wild type, but not Ncf1-/- mice………46
3.8 Toluene diisocyanate exposure induces inflammatory cell infiltration in the lung………48
3.9 Different TDI-induced cytokine and specific antibody responses in wild type and Ncf1-/-mice………49
3.10 Different TDI-induced cytokine and specific antibody responses in wild type and Ncf1-/- mice……51
3.11 Toluene diisocyanate exposure induces redox-sensitive transcription factors translocation to nuclei…………53
3.12 CD4+ T cells and IL-17 are involved in TDI-induced lung inflammation…………54
Chapter 4 Discussion………………………………………………….……… 55
References………………………………………………………………………. 67
Appendix………………………………………………………………………...112

Figures legends
Figure 1. Sulfhydryl blockers inhibited the adhesion of HL-60 clone 15 cells to VCAM-1 by suppressing the active state of VLA-4………………… 76
Figure 2. Ligand-binding triggered the exposure of sulfhydryl groups on VLA-4 α4 chain………………………………………………………………..78
Figure 3. Redox modification of VLA-4 by exogenous ROS modulated its ligand-binding activity…………………………………………………80
Figure 4. Glutathione and hydrogen peroxide enhanced S-glutathionylation on α4 integrin and affect VLA-4ligand-binding………...……………………82
Figure 5. Glutathione and hydrogen peroxide regulated the cell rolling of HL-60 clone 15 on VCAM-1…………………………………………………84
Figure 6. Cytoskeleton reorganization and FAK signaling are involved in hydrogen peroxide-mediated modulation of VLA-4 integrin ligand-binding……………………………86
Figure 7. TDI exposure and leukocyte NADPH oxidase activity induced oxidant stress in the lung……………………………………………………….88
Figure 8. TDI exposure induced airway hyperresponsiveness in wild type, but not Ncf1-/- mice…………………………………………………………….97
Figure 9. Toluene diisocyanate exposure induced inflammatory cells infiltration in the lung……………………………………………………………..100
Figure 10. Different TDI-induced cytokine and specific antibody responses in wild type and Ncf1-/- mice…………………………………………….102
Figure 11. TDI exposure induced redox-sensitive transcription factor expression and translocation into nucleus in the lung……………………………104
Figure 12. CD4+ T cells, IL-17 and neutrophils are involved in TDI-induced lung inflammation…………………………………………………………107
Figure 13 working model 1. Very late antigen-4 integrin (VLA-4 integrin) is a redox sensitive adhesion molecule…………….109
Figure 14 working model 2. Leukocyte NADPH oxidase is required for toluene diisocyanate-induced lung inflammation.…………111
Alon, R., Kassner, P.D., Carr, M.W., Finger, E.B., Hemler, M.E., and Springer, T.A. (1995). The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. J Cell Biol 128, 1243-1253.
Balmes, J., Becklake, M., Blanc, P., Henneberger, P., Kreiss, K., Mapp, C., Milton, D., Schwartz, D., Toren, K., and Viegi, G. (2003). American Thoracic Society Statement: Occupational contribution to the burden of airway disease. Am J Respir Crit Care Med 167, 787-797.
Barrett, N.A., and Austen, K.F. (2009). Innate cells and T helper 2 cell immunity in airway inflammation. Immunity 31, 425-437.
Baur, X., Marek, W., Ammon, J., Czuppon, A.B., Marczynski, B., Raulf-Heimsoth, M., Roemmelt, H., and Fruhmann, G. (1994). Respiratory and other hazards of isocyanates. Int Arch Occup Environ Health 66, 141-152.
Bazzoni, G., Ma, L., Blue, M.L., and Hemler, M.E. (1998). Divalent cations and ligands induce conformational changes that are highly divergent among beta1 integrins. J Biol Chem 273, 6670-6678.
Beglova, N., Blacklow, S.C., Takagi, J., and Springer, T.A. (2002). Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation. Nat Struct Biol 9, 282-287.
Berlin, C., Bargatze, R.F., Campbell, J.J., von Andrian, U.H., Szabo, M.C., Hasslen, S.R., Nelson, R.D., Berg, E.L., Erlandsen, S.L., and Butcher, E.C. (1995). alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 80, 413-422.
Bernstein, J.A. (1996). Overview of diisocyanate occupational asthma. Toxicology 111, 181-189.
Bousquet, J., Chanez, P., Lacoste, J.Y., Barneon, G., Ghavanian, N., Enander, I., Venge, P., Ahlstedt, S., Simony-Lafontaine, J., Godard, P., et al. (1990). Eosinophilic inflammation in asthma. N Engl J Med 323, 1033-1039.
Boyce, J.A., Broide, D., Matsumoto, K., and Bochner, B.S. (2009). Advances in mechanisms of asthma, allergy, and immunology in 2008. J Allergy Clin Immunol 123, 569-574.
Brown, L.A., Ping, X.D., Harris, F.L., and Gauthier, T.W. (2007). Glutathione availability modulates alveolar macrophage function in the chronic ethanol-fed rat. Am J Physiol Lung Cell Mol Physiol 292, L824-832.
Butcher, E.C., and Picker, L.J. (1996). Lymphocyte homing and homeostasis. Science 272, 60-66.
Calvete, J.J., Henschen, A., and Gonzalez-Rodriguez, J. (1991). Assignment of disulphide bonds in human platelet GPIIIa. A disulphide pattern for the beta-subunits of the integrin family. Biochem J 274 ( Pt 1), 63-71.
Chan-Yeung, M., and Malo, J.L. (1995). Occupational asthma. N Engl J Med 333, 107-112.
Chan, B.M., Elices, M.J., Murphy, E., and Hemler, M.E. (1992). Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of alpha 4 beta 1 (VLA-4) and alpha 4 beta 7 on the human B cell line JY. J Biol Chem 267, 8366-8370.
Chen, C., Mobley, J.L., Dwir, O., Shimron, F., Grabovsky, V., Lobb, R.R., Shimizu, Y., and Alon, R. (1999). High affinity very late antigen-4 subsets expressed on T cells are mandatory for spontaneous adhesion strengthening but not for rolling on VCAM-1 in shear flow. J Immunol 162, 1084-1095.
Chigaev, A., Blenc, A.M., Braaten, J.V., Kumaraswamy, N., Kepley, C.L., Andrews, R.P., Oliver, J.M., Edwards, B.S., Prossnitz, E.R., Larson, R.S., et al. (2001). Real time analysis of the affinity regulation of alpha 4-integrin. The physiologically activated receptor is intermediate in affinity between resting and Mn(2+) or antibody activation. J Biol Chem 276, 48670-48678.
Chigaev, A., Buranda, T., Dwyer, D.C., Prossnitz, E.R., and Sklar, L.A. (2003). FRET detection of cellular alpha4-integrin conformational activation. Biophys J 85, 3951-3962.
Chuang, K.P., Huang, Y.F., Hsu, Y.L., Liu, H.S., Chen, H.C., and Shieh, C.C. (2004). Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species-dependent pathway. Blood 104, 4046-4053.
Chuang, K.P., Tsai, W.S., Wang, Y.J., and Shieh, C.C. (2003). Superoxide activates very late antigen-4 on an eosinophil cell line and increases cellular binding to vascular cell adhesion molecule-1. Eur J Immunol 33, 645-655.
Dalle-Donne, I., Aldini, G., Carini, M., Colombo, R., Rossi, R., and Milzani, A. (2006). Protein carbonylation, cellular dysfunction, and disease progression. J Cell Mol Med 10, 389-406.
Deschamps, F., Prevost, A., Lavaud, F., and Kochman, S. (1998). Mechanisms of occupational asthma induced by isocyanates. Ann Occup Hyg 42, 33-36.
Donnelly, R., Buick, J.B., and Macmahon, J. (2004). Occupational asthma after exposure to plaster casts containing methylene diphenyl diisocyanate. Occup Med (Lond) 54, 432-434.
Dragos, M., Jones, M., Malo, J.L., Ghezzo, H., and Gautrin, D. (2009). Specific antibodies to diisocyanate and work-related respiratory symptoms in apprentice car-painters. Occup Environ Med 66, 227-234.
Edwards, B.S., Curry, M.S., Southon, E.A., Chong, A.S., and Graf, L.H., Jr. (1995). Evidence for a dithiol-activated signaling pathway in natural killer cell avidity regulation of leukocyte function antigen-1: structural requirements and relationship to phorbol ester- and CD16-triggered pathways. Blood 86, 2288-2301.
Emelyanov, A., Fedoseev, G., Abulimity, A., Rudinski, K., Fedoulov, A., Karabanov, A., and Barnes, P.J. (2001). Elevated concentrations of exhaled hydrogen peroxide in asthmatic patients. Chest 120, 1136-1139.
Essex, D.W., and Li, M. (2003). Redox control of platelet aggregation. Biochemistry 42, 129-136.
Fitzpatrick, A.M., Teague, W.G., Holguin, F., Yeh, M., and Brown, L.A. (2009). Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress. J Allergy Clin Immunol 123, 146-152 e148.
Fujiwara, M., Hirose, K., Kagami, S., Takatori, H., Wakashin, H., Tamachi, T., Watanabe, N., Saito, Y., Iwamoto, I., and Nakajima, H. (2007). T-bet inhibits both TH2 cell-mediated eosinophil recruitment and TH17 cell-mediated neutrophil recruitment into the airways. J Allergy Clin Immunol 119, 662-670.
Ghezzi, P. (2005). Regulation of protein function by glutathionylation. Free Radic Res 39, 573-580.
Ginsberg, M.H., Partridge, A., and Shattil, S.J. (2005). Integrin regulation. Curr Opin Cell Biol 17, 509-516.
Grabovsky, V., Feigelson, S., Chen, C., Bleijs, D.A., Peled, A., Cinamon, G., Baleux, F., Arenzana-Seisdedos, F., Lapidot, T., van Kooyk, Y., et al. (2000). Subsecond induction of alpha4 integrin clustering by immobilized chemokines stimulates leukocyte tethering and rolling on endothelial vascular cell adhesion molecule 1 under flow conditions. J Exp Med 192, 495-506.
Hagenow, K., Gelderman, K.A., Hultqvist, M., Merky, P., Backlund, J., Frey, O., Kamradt, T., and Holmdahl, R. (2009). Ncf1-associated reduced oxidative burst promotes IL-33R+ T cell-mediated adjuvant-free arthritis in mice. J Immunol 183, 874-881.
Hellings, P.W., Kasran, A., Liu, Z., Vandekerckhove, P., Wuyts, A., Overbergh, L., Mathieu, C., and Ceuppens, J.L. (2003). Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma. Am J Respir Cell Mol Biol 28, 42-50.
Heyworth, P.G., Cross, A.R., and Curnutte, J.T. (2003). Chronic granulomatous disease. Curr Opin Immunol 15, 578-584.
Hynes, R.O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110, 673-687.
Irie, A., Kamata, T., and Takada, Y. (1997). Multiple loop structures critical for ligand binding of the integrin alpha4 subunit in the upper face of the beta-propeller mode 1. Proc Natl Acad Sci U S A 94, 7198-7203.
Izakovicova Holla, L., Kankova, K., and Znojil, V. (2009). Haplotype analysis of the NADPH oxidase p22 phox gene in patients with bronchial asthma. Int Arch Allergy Immunol 148, 73-80.
Jacob, C., Holme, A.L., and Fry, F.H. (2004a). The sulfinic acid switch in proteins. Org Biomol Chem 2, 1953-1956.
Jacob, C., Lancaster, J.R., and Giles, G.I. (2004b). Reactive sulphur species in oxidative signal transduction. Biochem Soc Trans 32, 1015-1017.
Jan, R.L., Chen, S.H., Chang, H.Y., Yeh, H.J., Shieh, C.C., and Wang, J.Y. (2008). Asthma-like syndrome in school children after accidental exposure to xylene and methylene diphenyl diisocyanate. J Microbiol Immunol Infect 41, 337-341.
Janssen-Heininger, Y.M., Poynter, M.E., Aesif, S.W., Pantano, C., Ather, J.L., Reynaert, N.L., Ckless, K., Anathy, V., van der Velden, J., Irvin, C.G., et al. (2009). Nuclear factor kappaB, airway epithelium, and asthma: avenues for redox control. Proc Am Thorac Soc 6, 249-255.
Kashiwagi, H., Tomiyama, Y., Tadokoro, S., Honda, S., Shiraga, M., Mizutani, H., Handa, M., Kurata, Y., Matsuzawa, Y., and Shattil, S.J. (1999). A mutation in the extracellular cysteine-rich repeat region of the beta3 subunit activates integrins alphaIIbbeta3 and alphaVbeta3. Blood 93, 2559-2568.
Kastelein, R.A., Hunter, C.A., and Cua, D.J. (2007). Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol 25, 221-242.
Kim, S.H., Park, H.J., Lee, C.M., Choi, I.W., Moon, D.O., Roh, H.J., Lee, H.K., and Park, Y.M. (2006). Epigallocatechin-3-gallate protects toluene diisocyanate-induced airway inflammation in a murine model of asthma. FEBS Lett 580, 1883-1890.
Kinnula, V.L., and Crapo, J.D. (2003). Superoxide dismutases in the lung and human lung diseases. Am J Respir Crit Care Med 167, 1600-1619.
Lahav, J., Gofer-Dadosh, N., Luboshitz, J., Hess, O., and Shaklai, M. (2000). Protein disulfide isomerase mediates integrin-dependent adhesion. FEBS Lett 475, 89-92.
Lahav, J., Wijnen, E.M., Hess, O., Hamaia, S.W., Griffiths, D., Makris, M., Knight, C.G., Essex, D.W., and Farndale, R.W. (2003). Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin alpha2beta1. Blood 102, 2085-2092.
Lantz, R.C., Lemus, R., Lange, R.W., and Karol, M.H. (2001). Rapid reduction of intracellular glutathione in human bronchial epithelial cells exposed to occupational levels of toluene diisocyanate. Toxicol Sci 60, 348-355.
Laragione, T., Bonetto, V., Casoni, F., Massignan, T., Bianchi, G., Gianazza, E., and Ghezzi, P. (2003). Redox regulation of surface protein thiols: identification of integrin alpha-4 as a molecular target by using redox proteomics. Proc Natl Acad Sci U S A 100, 14737-14741.
Lemiere, C., Romeo, P., Chaboillez, S., Tremblay, C., and Malo, J.L. (2002). Airway inflammation and functional changes after exposure to different concentrations of isocyanates. J Allergy Clin Immunol 110, 641-646.
Liddington, R.C., and Bankston, L.A. (2000). The structural basis of dynamic cell adhesion: heads, tails, and allostery. Exp Cell Res 261, 37-43.
Liu, S., Thomas, S.M., Woodside, D.G., Rose, D.M., Kiosses, W.B., Pfaff, M., and Ginsberg, M.H. (1999). Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses. Nature 402, 676-681.
Lobb, R.R., and Hemler, M.E. (1994). The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest 94, 1722-1728.
Louten, J., Boniface, K., and de Waal Malefyt, R. (2009). Development and function of TH17 cells in health and disease. J Allergy Clin Immunol 123, 1004-1011.
Luo, B.H., Carman, C.V., and Springer, T.A. (2007). Structural basis of integrin regulation and signaling. Annu Rev Immunol 25, 619-647.
Luo, B.H., Springer, T.A., and Takagi, J. (2004). A specific interface between integrin transmembrane helices and affinity for ligand. PLoS Biol 2, e153.
Luque, A., Gomez, M., Puzon, W., Takada, Y., Sanchez-Madrid, F., and Cabanas, C. (1996). Activated conformations of very late activation integrins detected by a group of antibodies (HUTS) specific for a novel regulatory region (355-425) of the common beta 1 chain. J Biol Chem 271, 11067-11075.
Macchiarulo, A., Costantino, G., Meniconi, M., Pleban, K., Ecker, G., Bellocchi, D., and Pellicciari, R. (2004). Insights into phenylalanine derivatives recognition of VLA-4 integrin: from a pharmacophoric study to 3D-QSAR and molecular docking analyses. J Chem Inf Comput Sci 44, 1829-1839.
Mapp, C.E., Fryer, A.A., De Marzo, N., Pozzato, V., Padoan, M., Boschetto, P., Strange, R.C., Hemmingsen, A., and Spiteri, M.A. (2002). Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates. J Allergy Clin Immunol 109, 867-872.
Matheson, J.M., Lange, R.W., Lemus, R., Karol, M.H., and Luster, M.I. (2001). Importance of inflammatory and immune components in a mouse model of airway reactivity to toluene diisocyanate (TDI). Clin Exp Allergy 31, 1067-1076.
Mieyal, J.J., Gallogly, M.M., Qanungo, S., Sabens, E.A., and Shelton, M.D. (2008). Molecular mechanisms and clinical implications of reversible protein S-glutathionylation. Antioxid Redox Signal 10, 1941-1988.
Moriarty-Craige, S.E., and Jones, D.P. (2004). Extracellular thiols and thiol/disulfide redox in metabolism. Annu Rev Nutr 24, 481-509.
Muller, W.A., and Randolph, G.J. (1999). Migration of leukocytes across endothelium and beyond: molecules involved in the transmigration and fate of monocytes. J Leukoc Biol 66, 698-704.
Nagata, M., Sedgwick, J.B., Vrtis, R., and Busse, W.W. (1999). Endothelial cells upregulate eosinophil superoxide generation via VCAM-1 expression. Clin Exp Allergy 29, 550-561.
Nakae, S., Komiyama, Y., Nambu, A., Sudo, K., Iwase, M., Homma, I., Sekikawa, K., Asano, M., and Iwakura, Y. (2002). Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity 17, 375-387.
Nel, A., Xia, T., Madler, L., and Li, N. (2006). Toxic potential of materials at the nanolevel. Science 311, 622-627.
Olofsson, P., Holmberg, J., Tordsson, J., Lu, S., Akerstrom, B., and Holmdahl, R. (2003). Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nat Genet 33, 25-32.
Olsson, L.M., Lindqvist, A.K., Kallberg, H., Padyukov, L., Burkhardt, H., Alfredsson, L., Klareskog, L., and Holmdahl, R. (2007). A case-control study of rheumatoid arthritis identifies an associated single nucleotide polymorphism in the NCF4 gene, supporting a role for the NADPH-oxidase complex in autoimmunity. Arthritis Res Ther 9, R98.
Park, H.S., Kim, S.R., and Lee, Y.C. (2009). Impact of oxidative stress on lung diseases. Respirology 14, 27-38.
Plow, E.F., Haas, T.A., Zhang, L., Loftus, J., and Smith, J.W. (2000). Ligand binding to integrins. J Biol Chem 275, 21785-21788.
Pujades, C., Teixido, J., Bazzoni, G., and Hemler, M.E. (1996). Integrin alpha 4 cysteines 278 and 717 modulate VLA-4 ligand binding and also contribute to alpha 4/180 formation. Biochem J 313 ( Pt 3), 899-908.
Rahman, I., Biswas, S.K., Jimenez, L.A., Torres, M., and Forman, H.J. (2005). Glutathione, stress responses, and redox signaling in lung inflammation. Antioxid Redox Signal 7, 42-59.
Rahman, I., Biswas, S.K., and Kode, A. (2006). Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol 533, 222-239.
Ridley, A.J., Schwartz, M.A., Burridge, K., Firtel, R.A., Ginsberg, M.H., Borisy, G., Parsons, J.T., and Horwitz, A.R. (2003). Cell migration: integrating signals from front to back. Science 302, 1704-1709.
Riedl, M.A., and Nel, A.E. (2008). Importance of oxidative stress in the pathogenesis and treatment of asthma. Curr Opin Allergy Clin Immunol 8, 49-56.
Rose, D.M., Grabovsky, V., Alon, R., and Ginsberg, M.H. (2001). The affinity of integrin alpha(4)beta(1) governs lymphocyte migration. J Immunol 167, 2824-2830.
Saetta, M., Di Stefano, A., Maestrelli, P., De Marzo, N., Milani, G.F., Pivirotto, F., Mapp, C.E., and Fabbri, L.M. (1992). Airway mucosal inflammation in occupational asthma induced by toluene diisocyanate. Am Rev Respir Dis 145, 160-168.
San Jose, G., Fortuno, A., Beloqui, O., Diez, J., and Zalba, G. (2008). NADPH oxidase CYBA polymorphisms, oxidative stress and cardiovascular diseases. Clin Sci (Lond) 114, 173-182.
Schnyder-Candrian, S., Togbe, D., Couillin, I., Mercier, I., Brombacher, F., Quesniaux, V., Fossiez, F., Ryffel, B., and Schnyder, B. (2006). Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med 203, 2715-2725.
Shi, M., Foo, S.Y., Tan, S.M., Mitchell, E.P., Law, S.K., and Lescar, J. (2007). A structural hypothesis for the transition between bent and extended conformations of the leukocyte beta2 integrins. J Biol Chem 282, 30198-30206.
Shimaoka, M., Takagi, J., and Springer, T.A. (2002). Conformational regulation of integrin structure and function. Annu Rev Biophys Biomol Struct 31, 485-516.
Shimo-Nakanishi, Y., Hasebe, T., Suzuki, A., Mochizuki, H., Nomiyama, T., Tanaka, Y., Nagaoka, I., Mizuno, Y., and Urabe, T. (2004). Functional effects of NAD(P)H oxidase p22(phox) C242T mutation in human leukocytes and association with thrombotic cerebral infarction. Atherosclerosis 175, 109-115.
Springer, T.A. (1994). Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76, 301-314.
Sumi, Y., Kyi, M., Miyazaki, Y., Ohtani, Y., Miyake, S., and Yoshizawa, Y. (2003). Cytokine mRNA expression in isocyanate-induced hypersensitivity pneumonitis. Respiration 70, 284-291.
Takada, Y., Elices, M.J., Crouse, C., and Hemler, M.E. (1989). The primary structure of the alpha 4 subunit of VLA-4: homology to other integrins and a possible cell-cell adhesion function. EMBO J 8, 1361-1368.
Takagi, J., Petre, B.M., Walz, T., and Springer, T.A. (2002). Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 110, 599-511.
Valstar, D.L., Schijf, M.A., Nijkamp, F.P., Bloksma, N., and Henricks, P.A. (2004). Glutathione-conjugated toluene diisocyanate causes airway inflammation in sensitised mice. Arch Toxicol 78, 533-539.
Vanoirbeek, J.A., Tarkowski, M., Ceuppens, J.L., Verbeken, E.K., Nemery, B., and Hoet, P.H. (2004). Respiratory response to toluene diisocyanate depends on prior frequency and concentration of dermal sensitization in mice. Toxicol Sci 80, 310-321.
Wegener, K.L., Partridge, A.W., Han, J., Pickford, A.R., Liddington, R.C., Ginsberg, M.H., and Campbell, I.D. (2007). Structural basis of integrin activation by talin. Cell 128, 171-182.
Wikman, H., Piirila, P., Rosenberg, C., Luukkonen, R., Kaaria, K., Nordman, H., Norppa, H., Vainio, H., and Hirvonen, A. (2002). N-Acetyltransferase genotypes as modifiers of diisocyanate exposure-associated asthma risk. Pharmacogenetics 12, 227-233.
Wisnewski, A.V., and Redlich, C.A. (2001). Recent developments in diisocyanate asthma. Curr Opin Allergy Clin Immunol 1, 169-175.
Xiong, J.P., Stehle, T., Goodman, S.L., and Arnaout, M.A. (2003). New insights into the structural basis of integrin activation. Blood 102, 1155-1159.
Yan, B., Hu, D.D., Knowles, S.K., and Smith, J.W. (2000). Probing chemical and conformational differences in the resting and active conformers of platelet integrin alpha(IIb)beta(3). J Biol Chem 275, 7249-7260.
Yan, B., and Smith, J.W. (2000). A redox site involved in integrin activation. J Biol Chem 275, 39964-39972.
Yan, B., and Smith, J.W. (2001). Mechanism of integrin activation by disulfide bond reduction. Biochemistry 40, 8861-8867.
Yang, G.X., and Hagmann, W.K. (2003). VLA-4 antagonists: potent inhibitors of lymphocyte migration. Med Res Rev 23, 369-392.
Yang, Z., Sharma, A.K., Marshall, M., Kron, I.L., and Laubach, V.E. (2009). NADPH oxidase in bone marrow-derived cells mediates pulmonary ischemia-reperfusion injury. Am J Respir Cell Mol Biol 40, 375-381.
Yauch, R.L., Felsenfeld, D.P., Kraeft, S.K., Chen, L.B., Sheetz, M.P., and Hemler, M.E. (1997). Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding. J Exp Med 186, 1347-1355.
Yednock, T.A., Cannon, C., Vandevert, C., Goldbach, E.G., Shaw, G., Ellis, D.K., Liaw, C., Fritz, L.C., and Tanner, L.I. (1995). Alpha 4 beta 1 integrin-dependent cell adhesion is regulated by a low affinity receptor pool that is conformationally responsive to ligand. J Biol Chem 270, 28740-28750.
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