Abstract
The 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.
Highlights
The 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
In this study we investigated whether mannose-binding lectin (MBL), which has structural and functional similarities with C1q and the ficolins, interacts with the pentraxins using C. albicans as a model pathogen
When we examined the interaction between the pentraxins and MBL using the ELISA platform as the read-out, we could demonstrate a direct interaction between MBL and PTX3 or SAP but not with C-reactive protein (CRP)
Summary
Unlike CRP and SAP, the major sources of PTX3 are different cell types of extrahepatic origin including myeloid, endothelial, and epithelial cells. Under normal conditions PTX3 is hardly detectable in human serum (Ͻ2 ng/ml), whereas it may be found in concentrations of 200 – 800 g/liter in response to inflammation [18] Both CRP and SAP are molecules originating from genes present on chromosome 1q23 [15]. It has been demonstrated that MBL plays an important role in the protection against C. albicans by enhancing complement activation and uptake in polymorphonuclear leukocytes (PMNs) [31]. Whether this involves accessory assistance from e.g. the pentraxins is unknown. To have a pathophysiological readout, we used C. albicans as a model of infection
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