title: The selective augmentation by recombinant human tumour necrosis factor-alpha of neutrophil responses to pathogenic Escherichia coli.
abstract: Endotoxin release may amplify the neutrophil (PMN) responses to bacterial infection through the release of monocyte-derived tumour necrosis factor (TNF). The present study was designed to assess the effect of recombinant human TNF-alpha (rhTNF-alpha) on the in vitro response of human PMN to two defined strains of pathogenic Escherichia coli. In the absence of rhTNF-alpha, a P-fimbriate strain caused significant release of the PMN secondary granule marker vitamin B12-binding protein (B12 BP), and a low level of release of leukotriene B4 (LTB4). Type 1-fimbriate strain 504, however, stimulated the release of the primary granule marker myeloperoxidase (MPO) and PMN chemiluminescence (CL), in addition to B12 BP and LTB4 release. Following rhTNF-alpha (10(-9) M) pretreatment, the release of LTB4 by PMN stimulated with the P-fimbriate strain was synergistically augmented, while B12 BP and MPO release were additively increased. In contrast, rhTNF-alpha did not significantly affect any of the responses by the type 1-fimbriate strain. These results suggest selectivity in the priming of PMN by rhTNF-alpha and confirm the independence of PMN responses to phagocytic stimuli.
authors.affiliation: Institute of Nephrology, University of Wales College of Medicine, Cardiff.
authors.forename: R
authors.initials: R
authors.lastname: Steadman
authors.forename: M M
authors.initials: MM
authors.lastname: Petersen
authors.forename: D
authors.initials: D
authors.lastname: Williams
authors.forename: N
authors.initials: N
authors.lastname: Matthews
authors.forename: J D
authors.initials: JD
authors.lastname: Williams
mesh_terms: D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology*; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014155:Transcobalamins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D011994:Recombinant Proteins; D014155:Transcobalamins; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D009195:Peroxidase