MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked.
Sci Rep
; 6: 31877, 2016 08 18.
Article
in En
| MEDLINE
| ID: mdl-27535802
ABSTRACT
MASP-3 was discovered 15 years ago as the third mannan-binding lectin (MBL)-associated serine protease of the complement lectin pathway. Lacking any verified substrate its role remained ambiguous. MASP-3 was shown to compete with a key lectin pathway enzyme MASP-2 for MBL binding, and was therefore considered to be a negative complement regulator. Later, knock-out mice experiments suggested that MASP-1 and/or MASP-3 play important roles in complement pro-factor D (pro-FD) maturation. However, studies on a MASP-1/MASP-3-deficient human patient produced contradicting results. In normal resting blood unperturbed by ongoing coagulation or complement activation, factor D is present predominantly in its active form, suggesting that resting blood contains at least one pro-FD activating proteinase that is not a direct initiator of coagulation or complement activation. We have recently showed that all three MASPs can activate pro-FD in vitro. In resting blood, however, using our previously evolved MASP-1 and MASP-2 inhibitors we proved that neither MASP-1 nor MASP-2 activates pro-FD. Other plasma proteinases, particularly MASP-3, remained candidates for that function. For this study we evolved a specific MASP-3 inhibitor and unambiguously proved that activated MASP-3 is the exclusive pro-FD activator in resting blood, which demonstrates a fundamental link between the lectin and alternative pathways.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Complement Factor D
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Complement Pathway, Alternative
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Complement Pathway, Mannose-Binding Lectin
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Enzyme Precursors
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Mannose-Binding Protein-Associated Serine Proteases
Limits:
Animals
/
Humans
Language:
En
Journal:
Sci Rep
Year:
2016
Type:
Article
Affiliation country:
Hungary