title: Hemarthrosis in hemophilic mice results in alterations in M1-M2 monocyte/macrophage polarization.
abstract: BACKGROUND
  Joint bleedings result in iron-mediated synovitis and cartilage destruction. Monocyte/macrophage polarization affects their role in iron homeostasis. This study evaluates the effects of hemarthrosis on monocyte/macrophage polarization.
  
  
  METHODS
  Using a murine hemophilia model of acute joint bleeding and flow cytometry, we evaluated monocyte/macrophage polarization in blood, spleen, synovium, and knee lavage at day 1, 2, and 7 following the induction of hemarthrosis.
  
  
  RESULTS
  Induction of hemarthrosis resulted in a transient shift of blood monocytes towards a M1 type (control 13 vs. 1847 counted cells at day 1; p<0.01), a temporary decrease of spleen M1 monocytes (control 2841 vs. 1086 counted cells at day 1; p=0.02), and a sustained decrease of spleen M2 red pulp macrophages (control 1853 vs. 673 counted cells at day 7; p=0.01). In addition, an increase in M1 (control 119 vs. 592 counted cells at day 1; p=0.04) and M2 (control 247 vs. 650 counted cells at day 1; p=0.02) synovial macrophages was noted. In the joint lavage, a temporary increase in M1 monocytes (control 20 vs. 125 counted cells at day 1; p=0.04) and a more sustained increase in M2 monocytes (control 73 vs. 186 counted cells at day 2; p<0.01) was observed.
  
  
  CONCLUSIONS
  This study demonstrates alterations in monocyte/macrophage polarization following hemarthrosis resulting in a blood monocyte M1 phenotype and a combined M1-M2 monocyte/macrophage phenotype in the joint. Based on the different capabilities of M1 and M2 cells, modulating polarization of distinct monocyte/macrophage populations might represent interesting prophylactic or therapeutic approaches for joint bleedings.
authors.affiliation: Rheumatology & Clinical Immunology, University Medical Center, Utrecht, The Netherlands; Hematology & Van Creveldkliniek, University Medical Center, Utrecht, The Netherlands. Electronic address: l.nieuwenhuizen@umcutrecht.nl.
authors.forename: Laurens
authors.initials: L
authors.lastname: Nieuwenhuizen
authors.affiliation: Hematology & Van Creveldkliniek, University Medical Center, Utrecht, The Netherlands.
authors.forename: Roger E G
authors.initials: RE
authors.lastname: Schutgens
authors.affiliation: Rheumatology & Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Katja
authors.initials: K
authors.lastname: Coeleveld
authors.affiliation: Rheumatology & Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Mastbergen
authors.affiliation: Hematology & Van Creveldkliniek, University Medical Center, Utrecht, The Netherlands.
authors.forename: Goris
authors.initials: G
authors.lastname: Roosendaal
authors.affiliation: Hematology & Van Creveldkliniek, University Medical Center, Utrecht, The Netherlands.
authors.forename: Douwe H
authors.initials: DH
authors.lastname: Biesma
authors.affiliation: Rheumatology & Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Floris P J G
authors.initials: FP
authors.lastname: Lafeber
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D006395:Hemarthrosis / Q000097:blood* / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*
keywords: M1-M2 polarization; hemarthrosis; hemophilia; macrophage; monocyte