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Updated: Jun 27, 2026

Blood Collection from the American Horseshoe Crab, Limulus Polyphemus
Published on: October 13, 2008
Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation
Shigeru Ariki1, Shusaku Takahara, Toshio Shibata
1Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan.
Horseshoe crab complement component C3 activation is initiated by lipopolysaccharide (LPS) via factor C. This process enhances host defense by opsonizing bacteria, crucial for invertebrate immunity.
Area of Science:
- Invertebrate immunology
- Complement system evolution
- Host-pathogen interactions
Background:
- The complement system is vital for host defense in vertebrates, with C3 playing a key role in pathogen opsonization.
- The molecular mechanisms of C3 activation in invertebrates are largely unknown.
Purpose of the Study:
- To elucidate the molecular activation mechanism of invertebrate C3.
- To characterize the role of factor C in horseshoe crab complement activation.
Main Methods:
- Isolation and characterization of horseshoe crab C3 (TtC3).
- Flow cytometry to assess bacterial opsonization.
- Evaluation of pathogen-associated molecular patterns (PAMPs) for TtC3 activation.
- Inhibition assays using anti-factor C antibodies.
Main Results:
- Horseshoe crab complement opsonizes both Gram-negative and Gram-positive bacteria.
- Lipopolysaccharide (LPS) strongly induces TtC3 activation, unlike other PAMPs.
- Factor C in hemolymph plasma acts as an LPS-responsive C3 convertase.
- Factor C directly catalyzes TtC3 activation on bacterial surfaces.
Conclusions:
- Factor C is the primary initiator of horseshoe crab complement activation in response to LPS.
- This mechanism highlights a selective complement response to Gram-negative bacteria via LPS recognition.
- The findings provide insights into the evolution of the complement system and invertebrate immunity.
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