title: Granulocyte-macrophage colony-stimulating factor induces activation and restores respiratory burst activity in monocytes from septic patients.
abstract: Monocyte activation in response to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was examined in vitro in septic shock patients. These monocytes exhibited a greater respiratory burst activity than monocytes from healthy subjects; the response to secondary stimulation with bacterial stimuli was attenuated. GM-CSF restored the ability of monocytes to respond appropriately to secondary stimulation. Expression of certain integrin adhesion molecules, L-selectin, and Fcgamma receptors was increased on monocytes of septic shock patients; expression of CD11c was reduced. GM-CSF up-regulated integrin expression and decreased L-selectin, FcgammaRII, and FcgammaRIII expression. Septic patients exhibited greater biologic activity of monocyte tissue factor than did healthy subjects. Priming monocytes with GM-CSF accelerated tissue factor activation following stimulation with lipopolysaccharide and bacterial culture supernatant. Certain parameters of monocyte function may be restored by exposure to GM-CSF. This benefit may be offset by an increase in monocyte procoagulant activity.
authors.affiliation: Department of Haematology, St Bartholomew's and Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, United Kingdom.
authors.forename: M A
authors.initials: MA
authors.lastname: Williams
authors.forename: S A
authors.initials: SA
authors.lastname: White
authors.forename: J J
authors.initials: JJ
authors.lastname: Miller
authors.forename: C
authors.initials: C
authors.lastname: Toner
authors.forename: S
authors.initials: S
authors.lastname: Withington
authors.forename: A C
authors.initials: AC
authors.lastname: Newland
authors.forename: S M
authors.initials: SM
authors.lastname: Kelsey
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D011961:Receptors, Fc / Q000032:analysis / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology*; D013925:Thromboplastin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D017077:Culture Media, Conditioned; D016167:Integrin alphaXbeta2; D016023:Integrins; D008070:Lipopolysaccharides; D011961:Receptors, Fc; D017452:Receptors, IgG; D019041:L-Selectin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013925:Thromboplastin