論文

査読有り 国際誌
2019年12月

The effect of a novel immunosuppressive drug, a PAK-2 inhibitor, on macrophage differentiation/polarization in a rat small intestinal transplantation model.

Transplant immunology
  • Tasuku Kodama
  • ,
  • Akira Maeda
  • ,
  • Pei-Chi Lo
  • ,
  • Yuki Noguchi
  • ,
  • Chiyoshi Toyama
  • ,
  • Yuichi Takama
  • ,
  • Takehisa Ueno
  • ,
  • Yuko Tazuke
  • ,
  • Hiroshi Eguchi
  • ,
  • Katsuyoshi Matsunami
  • ,
  • Shuji Miyagawa
  • ,
  • Hiroomi Okuyama

57
開始ページ
101246
終了ページ
101246
記述言語
英語
掲載種別
DOI
10.1016/j.trim.2019.101246

OBJECTIVE: PQA-18 (Prenylated quinolinecarboxylic acid-18) has been reported to be a novel immunosuppressant that attenuates the production of various cytokines, and the differentiation of macrophages by inhibiting PAK2. In this study, we investigated the function of this drug mainly on macrophages using a rat small intestinal transplant model. METHODS: Male Dark Agouti (DA) and Lewis rats (LEW), 7-9 weeks of age, were used as donor and recipient, respectively. Approximately 15 cm intestinal grafts were heterotopically transplanted to the recipient rats. The recipient rat was treated with PQA-18 (4 mg/kg/day) by intraperitoneal injection (ip) from postoperative day 1 for 2 weeks. The in vivo effects of this drug were evaluated based on changes in body weight, and the population of each type of blood cell. Mixed lymphocyte reaction (MLR) was also assessed, using the T cells from intestinal mesenteric lymph nodes (MLN) of the grafts on POD6. Total cells from MLN and graft Payer's patch (PP) were next collected on POD6, and the number of infiltrated macrophages was determined. RESULTS: While the survival time was 7.0 ± 0.77 days for the control group (n = 9), that for the PQA-18 group was 10.7 ± 1.26 days (n = 10) (p < .001). Histological examinations showed a relatively clear difference in the grafts for both groups. In addition, the MLR response was significantly lower in recipients treated with PQA-18, suggesting PQA-18 well suppressed the T cells. Moreover, while a significant increase of both MHC class II and CD11b/c positive cells, estimated as differentiated/polarized macrophages, in MLN & PP was observed in the control group, PQA-18-administration significantly suppressed the differentiation of macrophages in the MLN & PP. CONCLUSION: PQA-18 significantly prolonged the survival of the rats with intestinal grafts, and also suppressed the infiltration of lymphocytes, and macrophages to the grafts.

リンク情報
DOI
https://doi.org/10.1016/j.trim.2019.101246
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31526866

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