Complement regulator and disease

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Complement regulator and disease
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content

• 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

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Complement regulator

• Decay accelerating factorDAF
• Homologous restriction factor HRF20
• Membrane cofactor proteinMCP

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

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Spontaneous C3 activation
Generation of C3 convertase
D
H2O
B
C3
C3
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Lytic pathwayinsertion of lytic complex into
cell membrane
HRF20
C 9
C 9
C 9
C 9
C 9
C 9
C 9
C 9
C 9
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Expression of complement activation regulators in
rat pancreatic cells
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The first step
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The second step
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The third step
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Results

• Plasma amylase and lipase(6h later)
• Extent of pancreatic necrosis(6h later)
• Expression of complement activation
  regulatorsDAF,HRF,MCP(0,3,6,12,24h)

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After SAP model was set up GroupA Plasma
level of amylase and lipase--increasedExpression
of complement activation regulators-- decreased
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The severity of pancreatic necrosis was enhanced.
The serum level of amylase or lipase Was
decreased and the extent of pancreatic necrosis
was decreased
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The expression of DAF and CD59in pancreas
---increasing The expression of MCP--- not
change
Group B
The expression of DAF ----increasing The
expression of CD59 and MCP ---not change
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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.

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The diseases caused by complement regulators

• Defect of DAF and CD59 both cause Paroxysmal
  nocturnal hemoglobinuria (PNH)(???????????)

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

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The clinical symptom of PNH

• 1.Hemoglobulinouria (?????)
• 2.??????
• 3.Infection and thrombin formation

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Hemoglobulinouria
The appropriate PH for complement is
6.87.0. When sleeping, acidic products
accumulate, the PH of plasma decrease, inducing
hemolysis, so the symptom is more severe in the
morning.
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• Almost all patients of PNH anemia. It can develop
  into bone marrow fibrosis and acute leukoemia.

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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.

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The treatment of PNH

• Blood transfusion
• Control the attack of hemolysis
• Stimulate the production of blood cells

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Thank you!
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