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The Function Of Anti-CD20Monoclonal Antibody Take Precautions Against The Acute Humoral Rejection By Using Mouse Skin Transplantation Model

Posted on:2013-10-20Degree:MasterType:Thesis
Country:ChinaCandidate:G SongFull Text:PDF
GTID:2234330371983148Subject:Surgery
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Object:This study investigated the CD20monoclonal antibody on how toprevent acute humoral rejection in a mouse skin transplant model. The presentstudy confirmed that T lymphocytes play a leading role in the acute humoralrejection, and the B-lymphocytes and mature plasma cells produce antibodiesinvolved in humoral rejection.Due to the breadth of the immunosuppressant ofefficiency and clinical applications, kidney transplantation made significantprogress. Overall graft survival was significantly prolonged,and exclusion ofthe overall incidence rate was significantly lower. However, the current clinicalroutine use of anti-proliferative drugs, calcineurin inhibitors and hormone for Tlymphocyte-mediated cellular immunity, humoral immune inhibition muchlower than the inhibition of cellular immunity. Currently used clinical drug forB-lymphocytes less, how to clear the B-lymphocytes, inhibition of the role of Blymphocytes in the humoral rejection, the research focus of the transplantcenters at inland and abroad. Produced by B lymphocytes involved in humoralrejection of donor-specific antibodies for epithelial cells as targets of attack,resulting in antibody-mediated humoral rejection. Therefore, clear theRecipient’s B lymphocytes, antibodies and DSA become the focus ofprevention and treatment of antibody-mediated humoral rejection. Along within-depth study of B lymphocytes and its mechanism of action is confirmed thatthe CD20antigen molecule is expressed in pre-B lymphocytes and mature Blymphocyte surface transmembrane glycoprotein what is involved in theactivation of B lymphocytes and antigen recognition molecules. Anti-CD20monoclonal antibody has a higher affinity to Molecular CD20with the surface of B lymphocytes who destroy B lymphocyte via inducing apoptosis,antibody-dependent cell-mediated cytotoxicity and complement-mediated cellcytotoxicity. Therefore, the CD20monoclonal antibodies are a class ofbiological agents with unique biological role and plays an important role inantibody-mediated humoral rejection in transplant therapy.Method: A group of recipient mice were given intraperitoneal injection ofdonor spleen cell suspension, and then injected into another mice through themethod of tail vein injection, and another group was given anti-CD20monoclonal antibody mouse tail vein injection through the method of tail veininjection.Then we established allogeneic mouse tail-dorsal skintransplantation and Embedding vascular tissue in subcutaneous model,andobserved the skin graft survival situation after operation. Application Flowcytometry detection of mouse tail vein injection of anti-CD20monoclonalantibody mouse B lymphocytes, and cut the transplanted skin and vasculartissues for histopathological examination, and study the role of CD20monoclonal antibodies in antibody-mediated humoral rejectionthe.Results:(1) Control group of mice skin graft mean survival time (MST)was11.5days.The average MST of skin grafts of the mouse tail vein injection ofserogroups9days.The tail vein injection of anti-CD20monoclonal antibodygroup skin graft average MST was12.5days.(2) The percentage of spleen cells in flow cytometry tail vein injection ofanti-CD20monoclonal antibody group B lymphocytes (B220+). Comparedwith normal mice, the mouse tail vein injection of anti-CD20monoclonalantibody group B lymphocytes in a significant reduction (P <0.05).(3) Take three of spleen tissue HE staining pathology. Tail vein injectionof serum group than the control group germinal center in spleen tissuessignificantly increased lymphocyte-intensive; tail vein injection of CD20 monoclonal antibody group compared with the control significantly narrowedthe spleen small lymphocytes decreased significantly.(4) Take the recipient rats of skin grafts and vascular tissue HE stainingpathology. Tail vein injection of serum group compare with the control groupof skin grafts organizations and subcutaneous vascular tissue inflammatorycells and lymphocytes increased significantly, and the destruction of theorganizational structure is obvious. Vascular inflammatory response in the partof the vessel wall machine of serious vascular layers of tissue destruction andluminal blockage. Tail vein injection of CD20monoclonal antibody group ofskin grafts organization and subcutaneous vascular tissue inflammatory cellsand lymphocytes was significantly less than the control group, andorganizational structure destruction is not obvious. Vascular inflammatoryresponse in light,each layer group is more complete and lumen exists.Conclusions: By tail vein injection of anti-CD20monoclonal antibodygroup hours prolonged survival of skin grafts, preoperative use of anti-CD20monoclonal antibody is effective in preventing antibody-mediated acuterejection.
Keywords/Search Tags:Anti-CD20monoclonal antibody, B lymphocytes, Humoral rejection, allotransplantation, Flow cytometry, Skin transplantation
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