{"title":"环孢素A对巨噬细胞的体内作用。","authors":"Y Matsushima, T Baba","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>The macrophage disappearance reaction (MDR) was induced when muramyl dipeptide (MDP) was injected intraperitoneally into guinea pigs bearing macrophage-rich peritoneal exudate cells. Heparin could inhibit the MDR induced by MDP. In the present study, we tested the effect of the immunosuppressive agent cyclosporine A (CsA) on MDR. The MDR was significantly suppressed in guinea pigs given 20 or 100 mg/kg of CsA, although 5 mg/kg of CsA had no effect. The number of macrophages elicited by liquid paraffin was significantly reduced in guinea pigs given with 20 or 100 mg/kg of CsA, but not in those given 5 mg/kg of CsA. These results indicate that CsA could directly affect macrophages in vivo, through a relatively high dose was required. Cyclosporine A (CsA), a cyclic peptide of 11 amino acids, is a fungal metabolite with potent immunosuppressive properties. Numerous experimental and clinical trials have demonstrated its effectiveness in organ transplantation. It has been suggested that primary target cells of CsA were T-lymphocytes, and macrophages were not directly affected. However, recent studies in an in vitro system have shown that some functions of macrophage are affected by CsA. These include chemotaxis (Drath & Kahan, 1983), interleukin-1 generation (Bunjes et al., 1981), prostaglandin E production (Whisler et al., 1984) and procoagulant activity (Carlsen et al., 1985). However, the effect of CsA on macrophages has not been elucidated in vivo. The macrophage disappearance reaction (MDR) is an in vivo manifestation of cell-mediated immunity and/or delayed type hypersensitivity (Sonozaki et al., 1975). Furthermore, our previous study demonstrated a possibility that MDR was an in vivo manifestation of macrophage activation (Ochiya et al., 1982). Muramyl dipeptide (MDP; N-acetyl-muramyl-L-alanyl-D-isoglutamine), a synthetic analogue of water soluble components of bacterial cell wall peptidoglycans, is known to have the ability to activate macrophages (Nagao et al., 1979). In the present study, attempts were made to induce MDR by MDP and the effect of CsA on the MDR was studied.</p>","PeriodicalId":73745,"journal":{"name":"Journal of Experimental Pathology","volume":"5 2","pages":"39-48"},"PeriodicalIF":0.0000,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The in vivo effect of cyclosporine A on macrophages.\",\"authors\":\"Y Matsushima, T Baba\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The macrophage disappearance reaction (MDR) was induced when muramyl dipeptide (MDP) was injected intraperitoneally into guinea pigs bearing macrophage-rich peritoneal exudate cells. Heparin could inhibit the MDR induced by MDP. In the present study, we tested the effect of the immunosuppressive agent cyclosporine A (CsA) on MDR. The MDR was significantly suppressed in guinea pigs given 20 or 100 mg/kg of CsA, although 5 mg/kg of CsA had no effect. The number of macrophages elicited by liquid paraffin was significantly reduced in guinea pigs given with 20 or 100 mg/kg of CsA, but not in those given 5 mg/kg of CsA. These results indicate that CsA could directly affect macrophages in vivo, through a relatively high dose was required. Cyclosporine A (CsA), a cyclic peptide of 11 amino acids, is a fungal metabolite with potent immunosuppressive properties. Numerous experimental and clinical trials have demonstrated its effectiveness in organ transplantation. It has been suggested that primary target cells of CsA were T-lymphocytes, and macrophages were not directly affected. However, recent studies in an in vitro system have shown that some functions of macrophage are affected by CsA. These include chemotaxis (Drath & Kahan, 1983), interleukin-1 generation (Bunjes et al., 1981), prostaglandin E production (Whisler et al., 1984) and procoagulant activity (Carlsen et al., 1985). However, the effect of CsA on macrophages has not been elucidated in vivo. The macrophage disappearance reaction (MDR) is an in vivo manifestation of cell-mediated immunity and/or delayed type hypersensitivity (Sonozaki et al., 1975). Furthermore, our previous study demonstrated a possibility that MDR was an in vivo manifestation of macrophage activation (Ochiya et al., 1982). Muramyl dipeptide (MDP; N-acetyl-muramyl-L-alanyl-D-isoglutamine), a synthetic analogue of water soluble components of bacterial cell wall peptidoglycans, is known to have the ability to activate macrophages (Nagao et al., 1979). In the present study, attempts were made to induce MDR by MDP and the effect of CsA on the MDR was studied.</p>\",\"PeriodicalId\":73745,\"journal\":{\"name\":\"Journal of Experimental Pathology\",\"volume\":\"5 2\",\"pages\":\"39-48\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1990-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Experimental Pathology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Experimental Pathology","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
将muramyl dipeptide (MDP)腹腔注射到富含巨噬细胞的豚鼠腹膜渗出细胞中,诱导巨噬细胞消失反应(MDR)。肝素对MDP诱导的MDR有抑制作用。在本研究中,我们测试了免疫抑制剂环孢素A (CsA)对MDR的作用。在给予20或100 mg/kg CsA的豚鼠中,MDR被显著抑制,尽管5 mg/kg CsA没有影响。CsA剂量为20或100 mg/kg的豚鼠液体石蜡诱导的巨噬细胞数量明显减少,而CsA剂量为5 mg/kg的豚鼠液体石蜡诱导的巨噬细胞数量明显减少。这些结果表明,CsA在体内可以直接影响巨噬细胞,但需要较高的剂量。环孢素A (Cyclosporine A, CsA)是一种由11个氨基酸组成的环状肽,是一种真菌代谢产物,具有有效的免疫抑制特性。大量的实验和临床试验证明了其在器官移植中的有效性。有研究表明,CsA的主要靶细胞是t淋巴细胞,巨噬细胞不受直接影响。然而,最近在体外系统的研究表明,巨噬细胞的一些功能受到CsA的影响。这些包括趋化性(Drath & Kahan, 1983)、白细胞介素-1生成(Bunjes等,1981)、前列腺素E生成(whistler等,1984)和促凝活性(Carlsen等,1985)。然而,CsA对巨噬细胞的体内作用尚未得到证实。巨噬细胞消失反应(MDR)是细胞介导免疫和/或延迟型超敏反应的体内表现(Sonozaki et al., 1975)。此外,我们之前的研究表明MDR可能是巨噬细胞激活的一种体内表现(Ochiya et al., 1982)。Muramyl二肽;n -乙酰-muramyl- l- alanyl- d -异谷氨酰胺)是细菌细胞壁肽聚糖水溶性成分的合成类似物,已知具有激活巨噬细胞的能力(Nagao et al., 1979)。本研究尝试用MDP诱导MDR,并研究了CsA对MDR的影响。
The in vivo effect of cyclosporine A on macrophages.
The macrophage disappearance reaction (MDR) was induced when muramyl dipeptide (MDP) was injected intraperitoneally into guinea pigs bearing macrophage-rich peritoneal exudate cells. Heparin could inhibit the MDR induced by MDP. In the present study, we tested the effect of the immunosuppressive agent cyclosporine A (CsA) on MDR. The MDR was significantly suppressed in guinea pigs given 20 or 100 mg/kg of CsA, although 5 mg/kg of CsA had no effect. The number of macrophages elicited by liquid paraffin was significantly reduced in guinea pigs given with 20 or 100 mg/kg of CsA, but not in those given 5 mg/kg of CsA. These results indicate that CsA could directly affect macrophages in vivo, through a relatively high dose was required. Cyclosporine A (CsA), a cyclic peptide of 11 amino acids, is a fungal metabolite with potent immunosuppressive properties. Numerous experimental and clinical trials have demonstrated its effectiveness in organ transplantation. It has been suggested that primary target cells of CsA were T-lymphocytes, and macrophages were not directly affected. However, recent studies in an in vitro system have shown that some functions of macrophage are affected by CsA. These include chemotaxis (Drath & Kahan, 1983), interleukin-1 generation (Bunjes et al., 1981), prostaglandin E production (Whisler et al., 1984) and procoagulant activity (Carlsen et al., 1985). However, the effect of CsA on macrophages has not been elucidated in vivo. The macrophage disappearance reaction (MDR) is an in vivo manifestation of cell-mediated immunity and/or delayed type hypersensitivity (Sonozaki et al., 1975). Furthermore, our previous study demonstrated a possibility that MDR was an in vivo manifestation of macrophage activation (Ochiya et al., 1982). Muramyl dipeptide (MDP; N-acetyl-muramyl-L-alanyl-D-isoglutamine), a synthetic analogue of water soluble components of bacterial cell wall peptidoglycans, is known to have the ability to activate macrophages (Nagao et al., 1979). In the present study, attempts were made to induce MDR by MDP and the effect of CsA on the MDR was studied.