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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