Chronic elevation of plasma thioredoxin: Inhibition of chemotaxis and curtailment of life expectancy in AIDS
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- Hajime Nakamura
- Department of Genetics, Stanford University Medical School, Stanford, CA 94305-5318; Department of Biological Responses, Institute of Virus Research, Kyoto University, Kyoto 606-8397, Japan; Department of Medical Biochemistry and Biophysics, Medical Nobel Institute for Biochemistry, Karolinska Institutet, SE-171 77 Stockholm, Sweden; and Department of Biochemistry, Istituto Mario Negri, 20157 Milan, Italy
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- Stephen C. De Rosa
- Department of Genetics, Stanford University Medical School, Stanford, CA 94305-5318; Department of Biological Responses, Institute of Virus Research, Kyoto University, Kyoto 606-8397, Japan; Department of Medical Biochemistry and Biophysics, Medical Nobel Institute for Biochemistry, Karolinska Institutet, SE-171 77 Stockholm, Sweden; and Department of Biochemistry, Istituto Mario Negri, 20157 Milan, Italy
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- Junji Yodoi
- Department of Genetics, Stanford University Medical School, Stanford, CA 94305-5318; Department of Biological Responses, Institute of Virus Research, Kyoto University, Kyoto 606-8397, Japan; Department of Medical Biochemistry and Biophysics, Medical Nobel Institute for Biochemistry, Karolinska Institutet, SE-171 77 Stockholm, Sweden; and Department of Biochemistry, Istituto Mario Negri, 20157 Milan, Italy
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- Arne Holmgren
- Department of Genetics, Stanford University Medical School, Stanford, CA 94305-5318; Department of Biological Responses, Institute of Virus Research, Kyoto University, Kyoto 606-8397, Japan; Department of Medical Biochemistry and Biophysics, Medical Nobel Institute for Biochemistry, Karolinska Institutet, SE-171 77 Stockholm, Sweden; and Department of Biochemistry, Istituto Mario Negri, 20157 Milan, Italy
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- Pietro Ghezzi
- Department of Genetics, Stanford University Medical School, Stanford, CA 94305-5318; Department of Biological Responses, Institute of Virus Research, Kyoto University, Kyoto 606-8397, Japan; Department of Medical Biochemistry and Biophysics, Medical Nobel Institute for Biochemistry, Karolinska Institutet, SE-171 77 Stockholm, Sweden; and Department of Biochemistry, Istituto Mario Negri, 20157 Milan, Italy
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- Leonard A. Herzenberg
- Department of Genetics, Stanford University Medical School, Stanford, CA 94305-5318; Department of Biological Responses, Institute of Virus Research, Kyoto University, Kyoto 606-8397, Japan; Department of Medical Biochemistry and Biophysics, Medical Nobel Institute for Biochemistry, Karolinska Institutet, SE-171 77 Stockholm, Sweden; and Department of Biochemistry, Istituto Mario Negri, 20157 Milan, Italy
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- Leonore A. Herzenberg
- Department of Genetics, Stanford University Medical School, Stanford, CA 94305-5318; Department of Biological Responses, Institute of Virus Research, Kyoto University, Kyoto 606-8397, Japan; Department of Medical Biochemistry and Biophysics, Medical Nobel Institute for Biochemistry, Karolinska Institutet, SE-171 77 Stockholm, Sweden; and Department of Biochemistry, Istituto Mario Negri, 20157 Milan, Italy
抄録
<jats:p>Thioredoxin (Trx) is an intracellular redox protein with extracellular cytokine-like and chemokine-like activities. We show here that, although plasma Trx levels are unrelated to survival of HIV-infected individuals with CD4 cell counts above 200/μl blood, survival is significantly impaired (<jats:italic>P</jats:italic>= 0.003) when plasma Trx is chronically elevated in HIV-infected subjects with CD4 T cell counts below this level (i.e., with Centers for Disease Control (CDC)-defined AIDS). Relevant to the mechanism potentially underlying this finding, we also present data from experimental studies in mice showing that elevated plasma Trx efficiently blocks lipopolysaccharide (LPS)-induced chemotaxis, an innate immune mechanism that is particularly crucial when adaptive immunity is compromised. Thus, we propose that elevated plasma Trx in HIV-infected individuals with low CD4 T cell counts directly impairs survival by blocking pathogen-induced chemotaxis, effectively eliminating the last (innate) barrier against establishment of opportunistic and other infections in these immunodeficient individuals.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 98 (5), 2688-2693, 2001-02-27
Proceedings of the National Academy of Sciences
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詳細情報 詳細情報について
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- CRID
- 1361418520221652864
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- NII論文ID
- 80012437186
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- ISSN
- 10916490
- 00278424
- http://id.crossref.org/issn/00278424
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