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

Complement Complement regulator regulator

and diseaseand disease

Complement Complement regulator regulator

and diseaseand disease

MEMBERS: 刘婷婷 孙满意 李晓露 宗广鑫 张桂 李刚

1. Complement 1. Complement regulatorsregulators and functions and functions

2. Effect of IL-4 on expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis.

3. The 3. The diseasesdiseases associated with complem associated with complement regulatorsent regulators

contentcontent

Complement regulatorDecay 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

H2O

iB

D

C3

C3a

b

Generation of C3 convertase

b DA

F

Lytic pathway:insertion of lytic complex into cell membrane

C8

C9

C9

C9

C9C9

C9 C

9C9

C9

HRF20

C 5 b

C 6

C 7

Expression of complement activation regulators in rat pancreatic cells

60 rats

Group A Group B Group 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 stepA

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-- decrease

d

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 The diseases caused by complement regulatorscomplement 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 cel

ls

MEMBERS: 刘婷婷 孙满意 李晓露

宗广鑫 张桂 李刚