title: Whole blood model of meningococcal bacteraemia--a method for exploring host-bacterial interactions.
abstract: An ex vivo whole blood model of meningococcal bacteraemia was developed to examine the total bactericidal activity of blood. Using a single defined donor and strains belonging to serogroups A, B and C and an unencapsulated strain, we demonstrated that the bactericidal mechanisms operating in whole blood varied with anticoagulant, serogroup and bacterial growth conditions. The choice of anticoagulant had a major effect on the survival of the serogroup A strain with 94% (SEM 7.6) survival in citrated blood compared to 19.7% (SEM 19.6) survival in heparinised blood after 60 min incubation. The serogroup C strain showed enhanced survival when grown in liquid medium compared to growth on solid medium (73.5%, SEM 7.5, and 8.2%, SEM 3.1, respectively, in citrated blood after 60 min). The pattern of survival of serogroup B and the unencapsulated strain were largely unaffected by these variables. Comparison with cell free conditions allowed the contribution of cellular components in meningococcal killing to be determined. Secreted levels of tumour necrosis factor and neutrophil elastase secreted during whole blood assays did not correlate with bacterial growth or viability indicating a lack of relationship between killing and activation of phagocytes.
authors.affiliation: Department of Medical Microbiology, St. Mary's Hospital Medical School, Paddington, London, U.K.
authors.forename: C A
authors.initials: CA
authors.lastname: Ison
authors.forename: R S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: N J
authors.initials: NJ
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Peakman
authors.forename: M
authors.initials: M
authors.lastname: Levin
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D016470:Bacteremia / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002474:Cell-Free System; D006790:Host-Parasite Interactions; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008589:Meningococcal Infections / Q000276:immunology*; D008954:Models, Biological; D009345:Neisseria meningitidis / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D018375:Neutrophil Activation; D010196:Pancreatic Elastase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D014409:Tumor Necrosis Factor-alpha; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase