Role of leucocyte integrins in phagocyte responses to granulocyte-macrophage colony stimulating factor (GM-CSF): in vitro and in vivo studies on leucocyte adhesion deficiency neutrophils.
The role of leucocyte integrins in phagocyte function has been studied by comparing normal neutrophils with those from a patient with partial leucocyte adhesion deficiency (LAD), in whom the levels of CD11b and CD11c were 10% of controls, whereas CD11a levels were normal. Unstimulated LAD neutrophils exhibited defective adhesion to plastic (4.4 +/- 1.5% cf. 14.4 +/- 3.8% in controls), but not to human umbilical vein endothelial cells (HUVECs). The adhesion to HUVECs could be further upregulated by granulocyte-macrophage colony stimulating factor (GM-CSF), but not by 12-O-tetradecanoylphorbol 13-acetate (TPA) which, in normal cells, is a more potent 'pro-adhesive agonist'. The normal neutrophil-endothelial interaction induced by GM-CSF in LAD neutrophils was confirmed in vivo when administration of GM-CSF resulted in rapid phagocyte margination. Neutrophil migration and phagocytosis/killing were defective in LAD neutrophils, and some improvement in phagocytosis/killing was seen following in vivo administration of GM-CSF. These studies illustrate that the degree to which the leucocyte integrins mediate adherence-related phagocyte functions varies not only with the particular function, but also with the conditions of stimulation. High levels of CD11b and CD11c expression appear not to be required for unstimulated or GM-CSF-stimulated neutrophil-endothelial interactions, either in vitro or in vivo. Other neutrophil functions, on the other hand, such as migration and phagocytosis/killing are much more dependent on the leucocyte integrins.
Yong
K
K
Department of Haematology, University College and Middlesex School of Medicine, London.
Addison
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IE
Johnson
B
B
Webster
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AD
Linch
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DC
D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D018845:CD11 Antigens; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002648:Child; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D016023:Integrins / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010585:Phagocyte Bactericidal Dysfunction / Q000276:immunology* / Q000628:therapy; D010587:Phagocytosis / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018845:CD11 Antigens; D016023:Integrins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor