Analysis of immunosupprative meclauism of Lipocortiut in tuwcr-beurig hestsits expression and action in wan

Research Project

Project/Area Number	04807090
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Digestive surgery
Research Institution	TOHOKU UNIVERSITY
Principal Investigator	OHTANI Haruo Tohoku University, 2nd Department of Pathology, Lecturer, 医学部, 助手 (30133987)
Co-Investigator(Kenkyū-buntansha)	SAITOH Yoshihiro Tohoku University, 1st Department of Surgery, Assistant, 医学部・附属病院, 助手 (10215569) SHIIBA Ken-ichi Tohoku University, 1st Department of Surgery, Lecturer, 医学部・附属病院, 講師 (90196345) 蝦名宣男仙北組合総合病院, 外科, 医師 (40185137)
Project Period (FY)	1992 – 1993
Project Status	Completed (Fiscal Year 1993)
Budget Amount *help	¥1,200,000 (Direct Cost: ¥1,200,000) Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000) Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Keywords	Lipocortin-1 / Immunosuppression / Cancer patient / サプレッサーマクロファージ
Research Abstract	In this study, we have explored the expression of Lipocortin-1(LC1)in the human tissues and its role in self-defense mechanism against cancers. The results are as follows ; 1)By immunohistochemical study using operative specimens, LC1 was proved in the cytoplasma of the inflammatory cells(mainly Macrophages)in the matrix of the tumor. 2)By FACS analysis, the rate of both LeuM3 and LC1 positive cells in peripheral blood mononuclear cells(PBMC)derived from cancer patients and healthy volunteers were 20% and 5% respectively. 3) By Westem blot analysis, LC1 protein whose molecule was 35 or 37 KDa was detected in the malignant ascites of gastric carcinoma patients. 4)Various concentrations of recombinant mouse LC1(gamma-LC1)were added to the cultures of PBMC to evaluate the effects on mitogenic responses(Con A)in healthy donors. The mitogenic responses in the presense of LC1(0.2, 2.0, 20mug/ml)were severely lower(10%, 90%, 99%)as compared to those without LC1. Furthermore, the similar inhib … More itory effects on mitogenic responses were obtained when malignant ascites or culture supernatents of spleen cells from cancer patients were added to the cultures instead of LC1.5)These inhibitory effects on the mitogenic responses were reversed by the addition of anti-LC1 serum. 6)Mitogenic responses of PBMC in cancer patients showed a decrease of 30% over healthy donors. Preparation of PBMC from cancer patients using nylonwool column in order to remove adherent cells reversed the response to normal level. In cancer patients, LC1 is produced distinctly and it seemed to be concerned in immunosuppression in tomor-bearing hosts because of the peculiar suppressive activities of LC1 in mitogenic responses. It is also suggested that LC1 is expressed strongly in accordance with progress of tumor in tomor-bearing mice, therefore we are now trying to clarify the relationship between expression of LC1 and progress of tumors in cancer patients with an effort to detect LC1 protein quantatively in human serum. Less