Complement regulator and disease MEMBERS: 刘婷婷 孙满意 李晓露 宗广鑫 张桂 李刚

1. Complement regulators and functions 2. Effect of IL-4 on expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis. 3. The diseases associated with complement regulators content

Complement regulator Decay accelerating factor—DAF Homologous restriction factor HRF20 Membrane cofactor protein—MCP

DAF -----binds to C4b and C3b, prevent formation of C3 convertase. HRF bind with C8, prevent the formation of MAC.

Spontaneous C3 activation C3 H2OH2O i B D C3a b Generation of C3 convertase b DAF

Lytic pathway: insertion of lytic complex into cell membrane C8 C9C9 C9C9 C9C9 C9C9 C9C9 C9C9 C9C9 C9C9 C9C9 HRF20 C 5 b C 6 C 7

Expression of complement activation regulators in rat pancreatic cells 60 rats Group AGroup BGroup C

Group A---Control group Group B Group C IL-4 (8 μg/animal) intraperitoneally The first step

The second step A B C injection of 5 ﹪ sodium taurocholate (1 mL/kg) into the pancreatic duct to induce severe acute pancreatitis ( SAP )

The third step A B C IL-4 (8 μg/animal) intraperitoneally

Results  Plasma amylase and lipase(6h later)  Extent of pancreatic necrosis(6h later)  Expression of complement activation regulators—DAF,HRF,MCP(0,3,6,12,24h)

After SAP model was set up: GroupA: Plasma level of amylase and lipase-- increased Expression of complement activation regulators-- decreased

A B C The severity of pancreatic necrosis was enhanced. The serum level of amylase or lipase Was decreased and the extent of pancreatic necrosis was decreased

The expression of DAF and CD59in pancreas ---increasing The expression of MCP--- not change Group B Group C The expression of DAF ---- increasing The expression of CD59 and MCP ---not change

CONCLUSION: Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Down regulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis.

The diseases caused by complement regulators Defect of DAF and CD59 both cause Paroxysmal nocturnal hemoglobinuria (PNH)( 阵发性睡眠性 血红蛋白尿 )

About PNH PNH patient has a mutation on pig — A gene. Red blood cell has DAF and lytic inhibitor deficiency, so the red blood cell is hypersensitive to complement.

Abnormal red blood cell can fix more C1, C1 attract more C3b. Red blood cell lack DAF, so more C5 is activated, form more MAC, induce hemolysis.

The clinical symptom of PNH 1.Hemoglobulinouria ( 血红蛋白尿 ) 2. 骨髓再生障碍 3.Infection and thrombin formation

Hemoglobulinouria The appropriate PH for complement is 6.8~7.0. When sleeping, acidic products accumulate, the PH of plasma decrease, inducing hemolysis, so the symptom is more severe in the morning.

骨髓再生障碍 Almost all patients of PNH anemia. It can develop into bone marrow fibrosis and acute leukoemia.

Infection and thrombin formation The number of neutrophil is decreased, inducing infection. The substance released by the lytic red blood cell promote the thrombin formation.

The treatment of PNH Blood transfusion Control the attack of hemolysis Stimulate the production of blood cells

MEMBERS: 刘婷婷 孙满意 李晓露 宗广鑫 张桂 李刚