• Ying Jie Ma, Andrea Doni, Mikkel-Ole Skjoedt, Christian Honoré, Maiken Arendrup, Alberto Mantovani, and Peter Garred.
• Laboratory of Molecular Medicine, Department of Clinical Immunology, Sect 7631, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
• J. Biol. Chem. 2011 Feb 4;286(5):3405-17.

AbstractThe long pentraxin 3 (PTX3), serum amyloid P component (SAP), and C-reactive protein belong to the pentraxin family of pattern recognition molecules involved in tissue homeostasis and innate immunity. They interact with C1q from the classical complement pathway. Whether this also occurs via the analogous mannose-binding lectin (MBL) from the lectin complement pathway is unknown. Thus, we investigated the possible interaction between MBL and the pentraxins. We report that MBL bound PTX3 and SAP partly via its collagen-like domain but not C-reactive protein. MBL-PTX3 complex formation resulted in recruitment of C1q, but this was not seen for the MBL-SAP complex. However, both MBL-PTX3 and MBL-SAP complexes enhanced C4 and C3 deposition and opsonophagocytosis of Candida albicans by polymorphonuclear leukocytes. Interaction between MBL and PTX3 led to communication between the lectin and classical complement pathways via recruitment of C1q, whereas SAP-enhanced complement activation occurs via a hitherto unknown mechanism. Taken together, MBL-pentraxin heterocomplexes trigger cross-activation of the complement system.

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