title: Differential augmentation by recombinant human tumor necrosis factor-alpha of neutrophil responses to particulate zymosan and glucan.
abstract: Zymosan (Z) and its major insoluble carbohydrate component beta-linked glucan activate human neutrophils (PMN) through a trypsin-sensitive recognition mechanism. This mechanism is believed to involve the PMN CR3R. Both Z and glucan generated dose and time-dependent release of the secondary lysosomal granule marker vitamin B12 binding protein, leukotriene B4 (LTB4) and superoxide from PMN and were phagocytosed with similar dose-dependent kinetics. The PMN superoxide and LTB4 responses to glucan; however, were consistently greater than those to the same doses of Z. The phagocytosis of both particles was significantly reduced after partial digestion with beta-laminarinase but not beta-glucosidase or alpha-mannosidase suggesting a recognition mechanism dependent on intact beta-1,3-glucosidic bonds in both particles. TNF-alpha (rhTNF-alpha) promoted a time- and dose-dependent increase in the expression of PMN CR3 up to 60 min. The increased expression of CR3 was paralleled by the release of the secondary lysosomal granule marker vitamin B12-binding protein. This granule contains a population of CR3R in its boundary membrane and it is the fusion of this membrane with the plasma membrane that may represent the mechanism by which CR3 expression is increased. Preincubation of PMN with 10(-9)M rhTNF-alpha augmented phagocytosis, LTB4, and superoxide generation by PMN in response to activation by Z. In contrast, none of the responses to glucan was significantly increased after incubation with rhTNF-alpha. These differences suggest a lack of absolute homology between the recognition mechanisms for zymosan and glucan and that there is a component of the recognition mechanism for zymosan that is independent of that for glucan and is up-regulated after rhTNF-alpha pretreatment.
authors.affiliation: Institute of Nephrology, University of Wales College of Medicine, Royal Infirmary, Cardiff, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Steadman
authors.forename: M M
authors.initials: MM
authors.lastname: Petersen
authors.forename: N
authors.initials: N
authors.lastname: Topley
authors.forename: D
authors.initials: D
authors.lastname: Williams
authors.forename: N
authors.initials: N
authors.lastname: Matthews
authors.forename: B
authors.initials: B
authors.lastname: Spur
authors.forename: J D
authors.initials: JD
authors.lastname: Williams
mesh_terms: D005936:Glucans / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011951:Receptors, Complement / Q000378:metabolism; D017463:Receptors, Complement 3b; D011994:Recombinant Proteins; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D014155:Transcobalamins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D005936:Glucans; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011994:Recombinant Proteins; D014155:Transcobalamins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007975:Leukotriene B4; D015054:Zymosan