PMID- 23305248 OWN - NLM STAT- MEDLINE DCOM- 20131112 LR - 20130910 IS - 1537-2995 (Electronic) IS - 0041-1132 (Linking) VI - 53 IP - 9 DP - 2013 Sep TI - Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model. PG - 1918-28 LID - 10.1111/trf.12068 [doi] AB - BACKGROUND: Platelet concentrate lysates (PCLs) are increasingly used in regenerative medicine. We have developed a solvent/detergent (S/D)-treated PCL. The functional properties of this preparation should be unveiled. We hypothesized that, due to transforming growth factor-beta1 (TGF-beta1) content, PCLs may exert immunosuppressive and anti-inflammatory functions. STUDY DESIGN AND METHODS: PCL was prepared by S/D treatment, oil extraction, and hydrophobic interaction chromatography. The content of TGF-beta in PCL was determined by enzyme-linked immunosorbent assay. Cultured CD4+ T cells were used to investigate the effects of PCL on expression of transcription factor forkhead box P3 (Foxp3), the inhibition of T-cell proliferation, and cytokine production. The regulatory function of PCL-converted CD4+ T cells was analyzed by suppressive assay. The BALB/c mice were given PCL-converted CD4+ T cells before ovalbumin (OVA) sensitization and challenge using an asthma model. Inflammatory parameters, such as the level of immunoglobulin E (IgE), airway hyperresponsiveness (AHR), bronchial lavage fluid eosinophils, and cytokines were assayed. Recombinant human (rHu) TGF-beta1 was used as control. RESULTS: PCL significantly enhanced the development of CD4+Foxp3+-induced regulatory T cells (iTregs). Converted iTregs produced neither Th1 nor Th2 cytokines and inhibited normal T-cell proliferation. PCL- and rHuTGF-beta-converted CD4+ T cells prevented OVA-induced asthma. PCL- and rHuTGF-beta-modified T cells both significantly reduced expression levels of OVA-specific IgE and significantly inhibited the development of AHR, airway eosinophilia, and Th2 responses in mice. CONCLUSION: S/D-treated PCL promotes Foxp3+ iTregs and exerts immunosuppressive and anti-inflammatory properties. This finding may help to understand the clinical properties of platelet lysates. CI - (c) 2013 American Association of Blood Banks. FAU - Lee, Yueh-Lun AU - Lee YL AD - Department of Microbiology and Immunology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan; Department of Pharmacology, College of Medicine, School of Medical Laboratory Science and Biotechnology, Taipei, Taiwan; College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; Department of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Family Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan; Research Department, Human Protein Process Science, Lille, France. FAU - Lee, Lin-Wen AU - Lee LW FAU - Su, Chen-Yao AU - Su CY FAU - Hsiao, George AU - Hsiao G FAU - Yang, Yi-Yuan AU - Yang YY FAU - Leu, Sy-Jye AU - Leu SJ FAU - Shieh, Ying-Hua AU - Shieh YH FAU - Burnouf, Thierry AU - Burnouf T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130111 PL - United States TA - Transfusion JT - Transfusion JID - 0417360 RN - 0 (Detergents) RN - 0 (Solvents) SB - IM MH - Animals MH - Asthma/immunology/metabolism/*therapy MH - Blood Platelets/drug effects/*virology MH - Detergents/pharmacology MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Mice MH - Platelet Transfusion MH - Solvents/pharmacology MH - T-Lymphocytes, Regulatory/*immunology EDAT- 2013/01/12 06:00 MHDA- 2013/11/13 06:00 CRDT- 2013/01/12 06:00 PHST- 2012/10/03 00:00 [received] PHST- 2012/11/07 00:00 [revised] PHST- 2012/11/12 00:00 [accepted] PHST- 2013/01/12 06:00 [entrez] PHST- 2013/01/12 06:00 [pubmed] PHST- 2013/11/13 06:00 [medline] AID - 10.1111/trf.12068 [doi] PST - ppublish SO - Transfusion. 2013 Sep;53(9):1918-28. doi: 10.1111/trf.12068. Epub 2013 Jan 11.