Role of cytosolic glucocorticoid receptor and Annexin‐A1 on neutrophil traffic from bone marrow into blood: SDF‐ 1alpha/CXCR‐4/CXCR‐2 axis

Abstract

AimsInvestigate the role of the glucocorticoid cytosolic receptor (GCR) and ANXA1 on neutrophil traffic between bone marrow (BM) and blood (PB), focusing on SDF1alpha/CXCR‐4/CXCR2 axis.MethodsBM perfusate and PB were collected from ANXA1‐ null (ANXA1−/−) and Balb/C wild‐type mice. Balb/C were pretreated with the GCR antagonist (RU38486; RU). Leukocyte numbers, CXCR‐2, CXCR‐4 and ANXA1 expressions, SDF‐1alpha and G‐CSF levels, chemotaxis, and phagocytosis of senescent neutrophils by BM macrophages were quantified.ResultsRU and ANXA1−/− presented accelerated granulocyte maturation in BM and neutrophilia, and ANXA1−/− showed increased number of mature granulocytes in BM. ANXA1 expression on BM neutrophils is reduced in RU. RU and ANXA1−/− presented increased CXCR‐4+ and reduced CXCR‐2+ cells in BM and PB, respectively. These cells presented reduced migration to SDF‐1alpha. BM SDF‐1‐alpha levels were reduced in ANXA1−/− and BM GCSF levels were reduced in RU and ANXA1−/−. BM macrophages collected from RU or ANXA1−/− phagocyted lesser number of senescent neutrophils.ConclusionEG, via GCR, and ANXA1 modulates the granulocyte maturation, neutrophil locomotion between BM/PB/BM and the phagocytosis of senescent neutrophils by BM macrophages.