Abstract
Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested. Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation. Although murine serum ficolin was shown to bind LPS in vitro, there was no difference between wildtype and ficolin deficient mice in morbidity and mortality by LPS-induced inflammation. Moreover, there was no difference between wildtype and ficolin deficient mice in the inflammatory cytokine profiles after LPS challenge. These findings were substantiated by microarray analysis revealing an unaltered spleen transcriptome profile in ficolin deficient mice compared to wildtype mice. Collectively, results from this study demonstrate that ficolins are not involved in host response to LPS-induced systemic inflammation.
Highlights
The ficolins are a family of pattern recognition molecules that initiate the lectin pathway of complement[1,2,3]
Plates coated with the ficolin-A ligand acetylated bovine serum albumin (AcBSA) served as a positive control while plates coated with Bovine serum albumin (BSA) served as a negative control
The results showed a dose-dependent binding of ficolin-A from WT serum to AcBSA and LPS (Fig. 1A,B)
Summary
The ficolins are a family of pattern recognition molecules that initiate the lectin pathway of complement[1,2,3]. C5b initiates formation of the lytic terminal membrane attack complex (C5b-9) In this way, effector functions of the complement cascade, i.e. opsonization, lysis and generation of an inflammatory response, result in elimination of the target. Sepsis is a systemic overwhelming inflammatory response, resulting from uncontrolled bacterial spread during infection, which can lead to tissue damage, multiple organ failure and death[25] Because this uncontrolled production of pro-inflammatory cytokines can be more damaging than the primary infection, it is important to attenuate this excessive reaction. Others have reported that ficolin-2 promotes production of pro-inflammatory cytokines in mouse macrophages in vitro, and that ficolin-A promotes TNF and IL-17 production in response to LPS in vivo[32] To elaborate on these previous discoveries and to better understand the role of ficolins during inflammation, we subjected ficolin deficient mice to LPS-induced inflammation and evaluated their inflammatory response and survival
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