title: Frontline Science: Splenic progenitors aid in maintaining high neutrophil numbers at sites of sterile chronic inflammation.
abstract: Neutrophils are constantly generated from hematopoietic stem and progenitor cells in the bone marrow to maintain high numbers in circulation. A considerable number of neutrophils and their progenitors have been shown to be present in the spleen too; however, their exact role in this organ remains unclear. Herein, we sought to study the function of splenic neutrophils and their progenitors using a mouse model for sterile, peritoneal inflammation. In this microcapsule device implantation model, we show chronic neutrophil presence at implant sites, with recruitment from circulation as the primary mechanism for their prevalence in the peritoneal exudate. Furthermore, we demonstrate that progenitor populations in the spleen play a key role in maintaining elevated neutrophil numbers. Our results provide new insight into the role for splenic neutrophils and their progenitors and establish a model to study neutrophil function during sterile inflammation.
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA;
authors.forename: Siddharth
authors.initials: S
authors.lastname: Jhunjhunwala
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA;
authors.forename: David
authors.initials: D
authors.lastname: Alvarez
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA;
authors.forename: Stephanie
authors.initials: S
authors.lastname: Aresta-DaSilva
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA;
authors.forename: Katherine
authors.initials: K
authors.lastname: Tang
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA;
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Tang
authors.affiliation: Department of Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA;
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA; and.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Newburger
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Harvard-Massachusetts Institute of Technology Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA;
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Harvard-Massachusetts Institute of Technology Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; dgander@mit.edu.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D019736:Prostheses and Implants / Q000009:adverse effects; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators
keywords: biomaterials; devices; granulocyte; hematopoietic stem cells; peritoneal cavity