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PMID:21957127

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Citation

Dalli, J, Jones, CP, Cavalcanti, DM, Farsky, SH, Perretti, M and Rankin, SM (2012) Annexin A1 regulates neutrophil clearance by macrophages in the mouse bone marrow. FASEB J. 26:387-96

Abstract

Under homeostatic conditions, a proportion of senescent CXCR4(hi) neutrophils home from the circulation back to the bone marrow, where they are phagocytosed by bone marrow macrophages. In this study, we have identified an unexpected role for the anti-inflammatory molecule annexin A1 (AnxA1) as a critical regulator of this process. We first observed that AnxA1(-/-) mice have significantly increased neutrophil numbers in their bone marrow while having normal levels of GM and G colony-forming units, monocytes, and macrophages. Although AnxA1(-/-) mice have more neutrophils in the bone marrow, a greater proportion of these cells are senescent, as determined by their higher levels of CXCR4 expression and annexin V binding. Consequently, bone marrow neutrophils from AnxA1(-/-) mice exhibit a reduced migratory capacity in vitro. Studies conducted in vitro also show that expression of AnxA1 is required for bone marrow macrophages, but not peritoneal macrophages, to phagocytose apoptotic neutrophils. Moreover, in vivo experiments indicate a defect in clearance of wild-type neutrophils in the bone marrow of AnxA1(-/-) mice. Thus, we conclude that expression of AnxA1 by resident macrophages is a critical determinant for neutrophil clearance in the bone marrow.

Links

PubMed PMC3250241 Online version:10.1096/fj.11-182089

Keywords

Animals; Annexin A1/genetics; Annexin A1/immunology; Annexin A1/metabolism; Bone Marrow/immunology; Bone Marrow/metabolism; Cell Aging/immunology; Chemotaxis/immunology; Gene Expression/immunology; Homeostasis/immunology; Macrophages, Peritoneal/immunology; Macrophages, Peritoneal/metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Neutrophils/immunology; Neutrophils/metabolism; Phagocytosis/immunology; Receptors, CXCR4/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ANXA1

involved_in

GO:0001780: neutrophil homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0002092)

Seeded From UniProt

complete

HUMAN:ANXA1

involved_in

GO:0097350: neutrophil clearance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0002092)

Seeded From UniProt

complete

MOUSE:ANXA1

involved_in

GO:0001780: neutrophil homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0002092)

Seeded From UniProt

complete

MOUSE:ANXA1

involved_in

GO:0033031: positive regulation of neutrophil apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0002476)

Seeded From UniProt

complete

HUMAN:ANXA1

involved_in

GO:0097350: neutrophil clearance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0002092)

Seeded From UniProt

complete

HUMAN:ANXA1

involved_in

GO:0001780: neutrophil homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0002092)

Seeded From UniProt

complete

MOUSE:ANXA1

involved_in

GO:0001780: neutrophil homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0002092)

Seeded From UniProt

complete

MOUSE:ANXA1

involved_in

GO:0033031: positive regulation of neutrophil apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0002476)

Seeded From UniProt

complete


See also

References

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