RRC ID 71626
著者 Toyama C, Maeda A, Kogata S, Takase K, Kodama T, Masahata K, Ueno T, Kamiyama M, Tazuke Y, Eguchi H, Matsunami K, Miyagawa S, Okuyama H.
タイトル Effect of a C5a receptor antagonist on macrophage function in an intestinal transplant rat model.
ジャーナル Transpl Immunol
Abstract BACKGROUND:C5a promotes alloreactivity via the C5a receptor 1 (C5aR1) on immune cells, but this has not been confirmed in the case of small intestine transplantation immunity. In the present study, we examined the effect of C5aR1 antagonist (PMX53) on macrophage function in small intestinal transplantation.
METHODS:The model was created by heterotopic intestinal transplantation using donor Dark Agouti and recipient Lewis rats. PMX53 was administered starting on the day of operation until postoperative day 7. The graft survivals were compared, and HE staining of grafts, lymphocyte mixed reaction test (MLR, mixed culture of T cells from lymph nodes and spleen cells from donors), and changes in macrophage and T cell accumulation in grafts on day 6 after transplantation were evaluated. In addition, the effect of PMX53 on macrophage differentiation and activation was assessed using macrophages derived from bone marrow (BMDM).
RESULTS:Graft survival was significantly prolonged in the therapeutic group compared to the untreated group. Histological evaluation showed that PMX53 inhibited the shortening of the graft villus, and the stimulation index of MLR was significantly lower in the therapeutic group compared to the untreated group. In the therapeutic group, the accumulation of macrophages in intestinal graft and monocyte in blood were reduced, compared with the untreated group. PMX53 decreased the differentiation in BMDM and the mRNA expression of IL-1β and TNF-α in activated BMDM.
CONCLUSION:Inhibition of C5a/C5aR1 signaling appears to regulate macrophage differentiation and suppress rejection in small intestine transplantation immunity.
巻・号 72
ページ 101559
公開日 2022-6-1
DOI 10.1016/j.trim.2022.101559
PII S0966-3274(22)00033-8
PMID 35227893
MeSH Animals Graft Survival Macrophages* Rats Rats, Inbred Lew Receptor, Anaphylatoxin C5a* / metabolism Signal Transduction
IF 1.624
リソース情報
ヒト・動物細胞 L929(RCB1422)