Regulation of macrophage activation by proteins expressed on apoptotic neutrophils: Subversion towards autoimmunity by proteinase 3

Nathalie Thieblemont, Véronique Witko-Sarsat, Amiram Ariel

Research output: Contribution to journalReview articlepeer-review


Neutrophils are critically involved in host defence and they also modulate the inflammatory process. Turning the inflammatory response towards a resolutive outcome requires a dialogue between apoptotic neutrophils and proresolving macrophages through complex key molecular interactions controlling efferocytosis, anti-inflammatory reprogramming and ultimately immune regulation. In this review, we will first focus on recent molecular analyses aiming at characterizing the role of proteins expressed on apoptotic neutrophils and their cognate partners expressed on macrophages in the resolution of inflammation. These will include chemokine receptors and their ligands and annexin A1 and its receptor FPR2. We will next depict how the structural and enzymatic properties of proteinase 3 (PR3), the autoantigen in vasculitis, allow its expression on apoptotic neutrophils, which in turn affects efferocytosis and immune response associated with the clearance of apoptotic cells. This example illustrates that the fate of apoptotic neutrophils directly influences the resolution of inflammation and immune responses thereby potentially contributing to systemic and nonresolving inflammation as well as autoimmunity.

Original languageEnglish
Article numbere12990
JournalEuropean Journal of Clinical Investigation
StatePublished - Nov 2018

Bibliographical note

Funding Information:
The authors greatly acknowledge the Investissements d'Avenir programme ANR‐11‐IDEX‐0005‐02, Sorbonne Paris Cité, Labex INFLAMEX, the DHU authors (AP-HP and Paris Descartes University), the Chancellerie des Universités de Paris Legs Poix and charities including, Arthritis Foundation, Vaincre la Mucoviscidose (VLM) and ABCF mucoviscidose. The manuscript was partially funded by the Israel Science Foundation, grant No. 678/13 to AA, by the Rosetrees Trust and the Wolfson Family Charitable Trust.

Publisher Copyright:
© 2018 Stichting European Society for Clinical Investigation Journal Foundation

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry


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