Expression of factor V by resident macrophages boosts host defense in the peritoneal cavity

Author:

Zhang Nan1ORCID,Czepielewski Rafael S.1ORCID,Jarjour Nicholas N.1ORCID,Erlich Emma C.1,Esaulova Ekaterina1ORCID,Saunders Brian T.1ORCID,Grover Steven P.2,Cleuren Audrey C.3ORCID,Broze George J.4,Edelson Brian T.1ORCID,Mackman Nigel2,Zinselmeyer Bernd H.1,Randolph Gwendalyn J.1ORCID

Affiliation:

1. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO

2. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC

3. Life Sciences Institute, University of Michigan, Ann Arbor, MI

4. Department of Medicine, Washington University School of Medicine, St. Louis, MO

Abstract

Macrophages resident in different organs express distinct genes, but understanding how this diversity fits into tissue-specific features is limited. Here, we show that selective expression of coagulation factor V (FV) by resident peritoneal macrophages in mice promotes bacterial clearance in the peritoneal cavity and serves to facilitate the well-known but poorly understood “macrophage disappearance reaction.” Intravital imaging revealed that resident macrophages were nonadherent in peritoneal fluid during homeostasis. Bacterial entry into the peritoneum acutely induced macrophage adherence and associated bacterial phagocytosis. However, optimal control of bacterial expansion in the peritoneum also required expression of FV by the macrophages to form local clots that effectively brought macrophages and bacteria in proximity and out of the fluid phase. Thus, acute cellular adhesion and resident macrophage–induced coagulation operate independently and cooperatively to meet the challenges of a unique, open tissue environment. These events collectively account for the macrophage disappearance reaction in the peritoneal cavity.

Funder

National Institutes of Heath

National Institute of Diabetes and Digestive and Kidney Diseases

American Heart Association

John C. Parker

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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