Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation

Shigeru Ariki, Shusaku Takahara, Toshio Shibata, Takaaki Fukuoka, Aya Ozaki, Yuichi Endo, Teizo Fujita, Takumi Koshiba, Shun-Ichiro Kawabata

研究成果: ジャーナルへの寄稿記事

45 引用 (Scopus)

抄録

The complement system in vertebrates plays an important role in host defense against and clearance of invading microbes, in which complement component C3 plays an essential role in the opsonization of pathogens, whereas the molecular mechanism underlying C3 activation in invertebrates remains unknown. In an effort to understand the molecular activation mechanism of invertebrate C3, we isolated and characterized an ortholog of C3 (designated TtC3) from the horseshoe crab Tachypleus tridentatus. Flow cytometric analysis using an Ab against TtC3 revealed that the horseshoe crab complement system opsonizes both Gram-negative and Gram-positive bacteria. Evaluation of the ability of various pathogen-associated molecular patterns to promote the proteolytic conversion of TtC3 to TtC3b in hemocyanin-depleted plasma indicated that LPS, but not zymosan, peptidoglycan, or laminarin, strongly induces this conversion, highlighting the selective response of the complement system to LPS stimulation. Although originally characterized as an LPS-sensitive initiator of hemolymph coagulation stored within hemocytes, we identified factor C in hemolymph plasma. An anti-factor C Ab inhibited various LPS-induced phenomena, including plasma amidase activity, the proteolytic activation of TtC3, and the deposition of TtC3b on the surface of Gram-negative bacteria. Moreover, activated factor C present on the surface of Gram-negative bacteria directly catalyzed the proteolytic conversion of the purified TtC3, thereby promoting TtC3b deposition. We conclude that factor C acts as an LPS-responsive C3 convertase on the surface of invading Gram-negative bacteria in the initial phase of horseshoe crab complement activation.

元の言語英語
ページ(範囲)7994-8001
ページ数8
ジャーナルJournal of Immunology
181
発行部数11
出版物ステータス出版済み - 12 1 2009

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Complement C3-C5 Convertases
Horseshoe Crabs
Complement Activation
Lipopolysaccharides
Gram-Negative Bacteria
Hemolymph
Invertebrates
amidase
Hemocytes
Hemocyanin
Complement C3
Zymosan
Peptidoglycan
Gram-Positive Bacteria
Vertebrates

All Science Journal Classification (ASJC) codes

  • Immunology

これを引用

Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation. / Ariki, Shigeru; Takahara, Shusaku; Shibata, Toshio; Fukuoka, Takaaki; Ozaki, Aya; Endo, Yuichi; Fujita, Teizo; Koshiba, Takumi; Kawabata, Shun-Ichiro.

:: Journal of Immunology, 巻 181, 番号 11, 01.12.2009, p. 7994-8001.

研究成果: ジャーナルへの寄稿記事

Ariki, S, Takahara, S, Shibata, T, Fukuoka, T, Ozaki, A, Endo, Y, Fujita, T, Koshiba, T & Kawabata, S-I 2009, 'Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation', Journal of Immunology, 巻. 181, 番号 11, pp. 7994-8001.
Ariki S, Takahara S, Shibata T, Fukuoka T, Ozaki A, Endo Y その他. Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation. Journal of Immunology. 2009 12 1;181(11):7994-8001.
Ariki, Shigeru ; Takahara, Shusaku ; Shibata, Toshio ; Fukuoka, Takaaki ; Ozaki, Aya ; Endo, Yuichi ; Fujita, Teizo ; Koshiba, Takumi ; Kawabata, Shun-Ichiro. / Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation. :: Journal of Immunology. 2009 ; 巻 181, 番号 11. pp. 7994-8001.
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abstract = "The complement system in vertebrates plays an important role in host defense against and clearance of invading microbes, in which complement component C3 plays an essential role in the opsonization of pathogens, whereas the molecular mechanism underlying C3 activation in invertebrates remains unknown. In an effort to understand the molecular activation mechanism of invertebrate C3, we isolated and characterized an ortholog of C3 (designated TtC3) from the horseshoe crab Tachypleus tridentatus. Flow cytometric analysis using an Ab against TtC3 revealed that the horseshoe crab complement system opsonizes both Gram-negative and Gram-positive bacteria. Evaluation of the ability of various pathogen-associated molecular patterns to promote the proteolytic conversion of TtC3 to TtC3b in hemocyanin-depleted plasma indicated that LPS, but not zymosan, peptidoglycan, or laminarin, strongly induces this conversion, highlighting the selective response of the complement system to LPS stimulation. Although originally characterized as an LPS-sensitive initiator of hemolymph coagulation stored within hemocytes, we identified factor C in hemolymph plasma. An anti-factor C Ab inhibited various LPS-induced phenomena, including plasma amidase activity, the proteolytic activation of TtC3, and the deposition of TtC3b on the surface of Gram-negative bacteria. Moreover, activated factor C present on the surface of Gram-negative bacteria directly catalyzed the proteolytic conversion of the purified TtC3, thereby promoting TtC3b deposition. We conclude that factor C acts as an LPS-responsive C3 convertase on the surface of invading Gram-negative bacteria in the initial phase of horseshoe crab complement activation.",
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AU - Ariki, Shigeru

AU - Takahara, Shusaku

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AU - Fukuoka, Takaaki

AU - Ozaki, Aya

AU - Endo, Yuichi

AU - Fujita, Teizo

AU - Koshiba, Takumi

AU - Kawabata, Shun-Ichiro

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AB - The complement system in vertebrates plays an important role in host defense against and clearance of invading microbes, in which complement component C3 plays an essential role in the opsonization of pathogens, whereas the molecular mechanism underlying C3 activation in invertebrates remains unknown. In an effort to understand the molecular activation mechanism of invertebrate C3, we isolated and characterized an ortholog of C3 (designated TtC3) from the horseshoe crab Tachypleus tridentatus. Flow cytometric analysis using an Ab against TtC3 revealed that the horseshoe crab complement system opsonizes both Gram-negative and Gram-positive bacteria. Evaluation of the ability of various pathogen-associated molecular patterns to promote the proteolytic conversion of TtC3 to TtC3b in hemocyanin-depleted plasma indicated that LPS, but not zymosan, peptidoglycan, or laminarin, strongly induces this conversion, highlighting the selective response of the complement system to LPS stimulation. Although originally characterized as an LPS-sensitive initiator of hemolymph coagulation stored within hemocytes, we identified factor C in hemolymph plasma. An anti-factor C Ab inhibited various LPS-induced phenomena, including plasma amidase activity, the proteolytic activation of TtC3, and the deposition of TtC3b on the surface of Gram-negative bacteria. Moreover, activated factor C present on the surface of Gram-negative bacteria directly catalyzed the proteolytic conversion of the purified TtC3, thereby promoting TtC3b deposition. We conclude that factor C acts as an LPS-responsive C3 convertase on the surface of invading Gram-negative bacteria in the initial phase of horseshoe crab complement activation.

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