title: Mitochondria and the lectin pathway of complement.
abstract: Mitochondria, the powerhouses of our cells, are remnants of a eubacterial endosymbiont. Notwithstanding the evolutionary time that has passed since the initial endosymbiotic event, mitochondria have retained many hallmarks of their eubacterial origin. Recent studies have indicated that during perturbations of normal homeostasis, such as following acute trauma leading to massive necrosis and release of mitochondria, the immune system might mistake symbiont for enemy and initiate an inappropriate immune response. The innate immune system is the first line of defense against invading microbial pathogens, and as such is the primary suspect in the recognition of mitochondria-derived danger-associated molecular patterns and initiation of an aberrant response. Conversely, innate immune mechanisms are also central to noninflammatory clearance of innocuous agents. Here we investigated the role of a central humoral component of innate immunity, the lectin pathway of complement, in recognition of mitochondria in vitro and in vivo. We found that the soluble pattern recognition molecules, mannan-binding lectin (MBL), L-ficolin, and M-ficolin, were able to recognize mitochondria. Furthermore, MBL in complex with MBL-associated serine protease 2 (MASP-2) was able to activate the lectin pathway and deposit C4 onto mitochondria, suggesting that these molecules are involved either in homeostatic clearance of mitochondria or in induction of untoward inflammatory reactions. We found that following mitochondrial challenge, C3 was consumed in vivo in the absence of overt inflammation, indicating a potential role of complement in noninflammatory clearance of mitochondria. Thus, we report here the first indication of involvement of the lectin pathway in mitochondrial immune handling.
authors: Department of Biomedicine, Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Christel R
authors: CR
authors: Brinkmann
authors: Department of Biomedicine, Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Lisbeth
authors: L
authors: Jensen
authors: Department of Biomedicine, Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Frederik
authors: F
authors: Dagnæs-Hansen
authors: Laboratory for Experimental Neuropathology, Department of Pathology, Randers Hospital, DK-8930 Randers NØ, Denmark; Institute of Clinical Medicine, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Ida E
authors: IE
authors: Holm
authors: Department of Immunology, Fukushima Medical University, 1-Hikariga-oka, Fukushima City, Fukushima 960-1295, Japan.
authors: Yuichi
authors: Y
authors: Endo
authors: Department of Immunology, Fukushima Medical University, 1-Hikariga-oka, Fukushima City, Fukushima 960-1295, Japan.
authors: Teizo
authors: T
authors: Fujita
authors: Department of Biomedicine, Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Steffen
authors: S
authors: Thiel
authors: Department of Biomedicine, Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Jens C
authors: JC
authors: Jensenius
authors: Department of Biomedicine, Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C, Denmark. Electronic address: sdegn@microbiology.au.dk.
authors: Søren E
authors: SE
authors: Degn
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D037582:Complement Pathway, Mannose-Binding Lectin; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000473:pathology; D037601:Mannose-Binding Lectin / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D000097604:Ficolins
chemical_list: D001798:Blood Proteins; D003176:Complement C3; D003181:Complement C4; D015850:Interleukin-6; D037102:Lectins; D008070:Lipopolysaccharides; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D051192:Receptors, Pattern Recognition; D000097604:Ficolins; C491338:Masp2 protein, rat
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