Ficolin-1-PTX3 complex formation promotes clearance of altered self-cells and modulates IL-8 production

Ying Jie Ma, Andrea Doni, Luigina Romani, Henrik Jessen Jurgensen, Niels Behrendt, Alberto Mantovani, Peter Garred

Research output: Contribution to journalArticlepeer-review

Abstract

The long pentraxin 3 (PTX3) has been shown to be important in maintaining internal tissue homeostasis and in protecting against fungal Aspergillus fumigatus infection. However, the molecular mechanisms of how these functions are elicited are poorly delineated. Ficolin-1 is a soluble pattern recognition molecule that interacts with PTX3. We hypothesized that heterocomplexes between ficolin-1 and PTX3 might mediate the signals necessary for sequestration of altered self-cells and A. fumigatus. We were able to show that ficolin-1 interacts with PTX3 via its fibrinogen-like domain. The interaction was affected in a pH- and divalent cation-sensitive manner. The primary binding site for ficolin-1 on PTX3 was located in the N-terminal domain portion of PTX3. Ficolin-1 and PTX3 heterocomplex formation occurred on dying host cells, but not on A. fumigatus. The heterocomplex formation was a prerequisite for enhancement of phagocytosis by human monocyte-derived macrophages and downregulation of IL-8 production during phagocytosis. On A. fumigatus, PTX3 exposed the C-terminal portion of the molecule, probably resulting in steric hindrance of ficolin-1 interaction with PTX3. These results demonstrate that ficolin-1 and PTX3 heterocomplex formation acts as a noninflammatory 'find me and eat me' signal to sequester altered-host cells. The fact that the ficolin-1-PTX3 complex formation did not occur on A. fumigatus shows that PTX3 uses different molecular effector mechanisms, depending on which domains it exposes during ligand interaction.

Original languageEnglish
Pages (from-to)1324-1333
Number of pages10
JournalJournal of Immunology
Volume191
Issue number3
DOIs
Publication statusPublished - Aug 1 2013

ASJC Scopus subject areas

  • Immunology

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