Impaired phagocytic mechanism in annexin 1 null macrophages.
The role of the anti-inflammatory protein annexin-A1 (Anx-A1) in the phagocytic process has been investigated using a murine bone marrow culture-derived macrophage model from Anx-A1(+/+) and Anx-A1(-/-) mice. Macrophages prepared from Anx-A1(-/-) mice exhibited a reduced ingestion of zymosan, Neisseria meningitidis or sheep red blood cells, when compared to Anx-A1(+/+) cells and in the case of zymosan this effect was also mirrored by a reduced clearance in vivo when particles were injected into the peritoneal cavity of Anx-A1(-/-) mice. The ablation of the Anx-A1 gene did not cause any apparent cytoskeletal defects associated with particle ingestion but the cell surface expression of the key adhesion molecule CD11b was depressed in the Anx-A1(-/-) cells providing a possible explanation for the attenuated phagocytic potential of these cells. The production of the cytokines TNFalpha and IL-6 was increased in Anx-A1(-/-) macrophages following phagocytosis of all types of particle.
Yona
Simon
S
Department of Biochemical Pharmacology, The William Harvey Research Institute, St Bartholomew's and the Royal London School of Medicine, University of London.
Heinsbroek
Sigrid E M
SE
Peiser
Leanne
L
Gordon
Siamon
S
Perretti
Mauro
M
Flower
Roderick J
RJ
D000818:Animals; D017305:Annexin A1 / Q000032:analysis / Q000502:physiology*; D039481:CD11b Antigen / Q000235:genetics; D005434:Flow Cytometry; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D010587:Phagocytosis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan / Q000378:metabolism
D017305:Annexin A1; D039481:CD11b Antigen; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan