Interactions of ficolin and mannose-binding lectin with fibrinogen/fibrin augment the lectin complement pathway.
Ficolin and mannose-binding lectin (MBL) are animal lectins that are involved in innate immunity by initiating the lectin complement pathway. Here, we report that interactions between these lectins and fibrinogen/fibrin augment the lectin pathway. An ELISA revealed that recombinant mouse ficolin A (rFcnA), rMBL-A and rMBL-C bind to fibrinogen in a dose-dependent manner. Affinity Western blotting showed that these lectins bind to the A alpha- and B beta-chains of fibrinogen and the alpha- and beta-chains of fibrin, but not to the gamma-chain, and that rMBL-A and rMBL-C preferentially bind to the alpha- and beta-chains. The C4 deposition activity on Fbg-coated plates was observed by using mouse serum, and the deposition on GlcNAc-coated plates was enhanced by fibrinogen supplementation and further enhanced by the addition of thrombin. Similar effects of fibrinogen and fibrin were observed in the bindings of these lectins to a Gram-positive pathogen, Staphylococcus aureus, and in the subsequent C3 deposition on the bacteria. In particular, the lectin pathway, through MBLs, seemed to synchronize with blood coagulation. Therefore, it is suggested that the lectin pathway collaborates with the coagulation system in the first-line host defense against pathogens under conditions such as injury and inflammation.
Endo
Yuichi
Y
Department of Immunology, Fukushima Medical University School of Medicine, Fukushima, Japan. yendo@fmu.ac.jp
Nakazawa
Naomi
N
Iwaki
Daisuke
D
Takahashi
Minoru
M
Matsushita
Misao
M
Fujita
Teizo
T
D000818:Animals; D001777:Blood Coagulation; D003176:Complement C3 / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D005337:Fibrin / Q000276:immunology*; D005340:Fibrinogen / Q000276:immunology*; D037102:Lectins / Q000235:genetics / Q000276:immunology*; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013211:Staphylococcus aureus / Q000276:immunology; D000097604:Ficolins
D003176:Complement C3; D003181:Complement C4; D005337:Fibrin; D005340:Fibrinogen; D037102:Lectins; D037601:Mannose-Binding Lectin; D000097604:Ficolins; C016759:C4b protein, mouse; C445639:Mbl2 protein, mouse; C069858:mannose binding protein A