RESUMO
It has been suggested that pyrogenic toxins of Staphylococcus aureus are involved in the series of events leading to some cases of sudden infant death syndrome (SIDS). The objectives of the study were to screen tissues from SIDS infants for pyrogenic toxins and to compare incidence of identification of these toxins among these infants from different countries. An enzyme-linked immunosorbent assay (ELISA) and a flow cytometry method were used to screen body fluids and frozen or formalin-fixed tissues for pyrogenic toxins of S. aureus, toxic shock syndrome toxin 1 (TSST), staphylococcal enterotoxins A (SEA), B (SEB), and C1 (SEC). Toxins were identified in tissues of 33/62 (53%) SIDS infants from three different countries: Scotland (10/ 19, 56%); France (7/13, 55%); Australia (16/30, 53%). In the Australian series, toxins were identified in only 3/19 (16%) non-SIDS deaths (chi2 = 5.42, P < 0.02). The flow cytometry method was useful for toxin detection in both frozen and fixed tissues, but ELISA was suitable only for frozen tissues or those fixed for less than 12 months. Identification of pyrogenic toxins in > 50% of SIDS infants from three different countries indicated further investigation into the role the toxins play in cot deaths might result in development of additional measures to reduce further the incidence of these infant deaths.
Assuntos
Toxinas Bacterianas , Enterotoxinas/análise , Staphylococcus aureus , Morte Súbita do Lactente/etiologia , Superantígenos , Encéfalo/microbiologia , Criança , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Formaldeído , Congelamento , Humanos , Lactente , Recém-Nascido , Rim/microbiologia , Baço/microbiologia , Staphylococcus aureus/isolamento & purificação , Fixação de TecidosRESUMO
Exposure to cigarette smoke is a major risk factor for sudden infant death syndrome and also for respiratory infections in children. It has been suggested that toxigenic bacteria colonizing the respiratory tract might play a role in some cases of sudden infant death syndrome and nicotine has been demonstrated to enhance the lethality of bacterial toxins in a model system. Pyrogenic toxins of Staphylococcus aureus have been identified in tissues of infants who died of sudden infant death syndrome. It has been suggested that some of these deaths were due to induction of inflammatory mediators by infectious agents during a period when infants are less able to control these responses. The aim of this study was to assess the effects of a water-soluble cigarette smoke extract on the production of tumor necrosis factor alpha and nitric oxide from human monocytes in response to staphylococcal toxic shock syndrome toxin 1 or infection of the monocytes with respiratory syncytial virus. Cell culture supernatants were examined by a bioassay using mouse fibroblasts (L-929 cell line) for tumor necrosis factor alpha activity and by a spectrophotometric method for nitrite. Compared with monocytes incubated with medium only, monocytes incubated with any of the factors or their combinations tested in the study released higher levels of tumor necrosis factor alpha and lower levels of nitric oxide. Incubation with cigarette smoke extract increased tumor necrosis factor alpha from respiratory syncytial virus-infected cells while it decreased tumor necrosis factor alpha from cells incubated with toxic shock syndrome toxin. Incubation with cigarette smoke extract decreased the nitric oxide production from respiratory syncytial virus-infected cells while it increased the nitric oxide production from cells incubated with toxic shock syndrome toxin. Monocytes from a minority of individuals demonstrated extreme tumor necrosis factor alpha responses and/or very high or very low nitric oxide. The proportion of samples in which extreme responses with a very high tumor necrosis factor alpha and very low nitric oxide were detected was increased in the presence of the three agents to 20% compared with 0% observed with toxic shock syndrome toxin 1 or 4% observed with cigarette smoke extract or respiratory syncytial virus.
Assuntos
Toxinas Bacterianas , Enterotoxinas/imunologia , Monócitos/metabolismo , Monócitos/virologia , Vírus Sinciciais Respiratórios/fisiologia , Fumaça/efeitos adversos , Morte Súbita do Lactente/etiologia , Superantígenos , Animais , Células Cultivadas , Humanos , Recém-Nascido , Camundongos , Monócitos/imunologia , Óxido Nítrico/biossíntese , Plantas Tóxicas , Fatores de Risco , Morte Súbita do Lactente/imunologia , Nicotiana , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Epidemiological evidence indicates infants immunised against diphtheria, pertussis and tetanus (DPT) are at decreased risk of sudden infant death syndrome (SIDS). Asymptomatic whooping cough and pyrogenic toxins of Staphylococcus aureus have been implicated in the aetiology of SIDS. The objectives of the present study were: (1) to determine if the DPT vaccine induced antibodies cross-reactive with the staphylococcal toxins; (2) to determine if antibodies to the pertussis toxin (PT) and the staphylococcal toxins were present in the sera of women during late pregnancy; (3) to examine the effects of infant immunisation on levels of antibodies to PT and the staphylococcal toxins; (4) to assess the effects of changes in immunisation schedules in the UK on the incidence and age distribution of SIDS. Enzyme-linked immunosorbent assays (ELISA) were used to measure binding of rabbit or human IgG to the DPT vaccine, PT, toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins A (SEA), B (SEB) and C (SEC). Neutralisation activity of anti-DPT serum was assessed by a bioassay for induction of nitric oxide from human monocytes by the staphylococcal toxins. Anti-DPT serum bound to the DPT vaccine, PT and each of the staphylococcal toxins. It also reduced the ability of the four toxins to induce nitric oxide from monocytes. In pregnant women, levels of IgG to PT, SEC and TSST-1 decreased significantly in relation to increasing weeks of gestation while antibodies to SEA and SEB increased. In infants' sera there were significant correlations between levels of IgG bound to DPT and IgG bound to PT, TSST-1 and SEC but not SEA or SEB. Antibody levels to the toxins in infants declined with age; sera from infants < or = 2 months of age had higher levels of IgG bound to the toxins than those older than 2 months. This pattern was observed for infants whose immunisation schedules began at 2 months of age or 3 months of age. The decrease in IgG bound to the toxins was, however, less for those immunised at 2 months. The decrease in SIDS deaths after the change in immunisation schedules was greatest in the 4-6-month age range. While DPT immunisation might prevent some unexplained infant deaths due to asymptomatic whooping cough, these data indicate that immunisation with DPT also induces antibodies cross-reactive with pyrogenic staphylococcal toxins implicated in many cases of SIDS. Passive immunisation of infants who have low levels of these antibodies might reduce further the numbers of these infant deaths.
Assuntos
Anticorpos Antibacterianos/sangue , Toxinas Bacterianas , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Enterotoxinas/imunologia , Staphylococcus aureus , Morte Súbita do Lactente/prevenção & controle , Superantígenos , Animais , Reações Cruzadas , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Esquemas de Imunização , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Masculino , Monócitos/metabolismo , Óxido Nítrico/biossíntese , Toxina Pertussis , Gravidez , Coelhos , Morte Súbita do Lactente/epidemiologia , Vacinação , Fatores de Virulência de Bordetella/imunologiaRESUMO
Cigarette smoke and virus infections contribute to the pathogenesis and exacerbation of chronic obstructive pulmonary disease and asthma. The objective of this study was to examine the effects of a water-soluble cigarette smoke extract (CSE) and/or respiratory syncytial virus (RSV) infection on release from monocytes of the blood from donors of tumour necrosis factor alpha (TNF-alpha) and nitric oxide (NO). Both RSV infection and CSE stimulated TNF-alpha release from monocytes and there was an additive effect if both the agents were present. There was a decrease in NO release, but the effect was significant only with CSE or a combination of CSE and RSV infection. Interferon gamma significantly increased TNF-alpha release and cotinine significantly increased NO release. Nicotine decreased both TNF-alpha and NO responses. The general pattern observed for individual donors was increased TNF-alpha and decreased NO. The proportion of extreme responses with very high TNF-alpha and very low NO in the presence of both RSV and CSE increased to 20% compared with 5% observed with CSE or RSV alone. The results show that RSV infection and components of cigarette smoke elicit inflammatory responses that could contribute to damage to the respiratory tract and these individual factors could be more harmful in combination.
Assuntos
Monócitos/imunologia , Nicotiana , Óxido Nítrico/metabolismo , Plantas Tóxicas , Vírus Sincicial Respiratório Humano/fisiologia , Fumaça , Fator de Necrose Tumoral alfa/metabolismo , Animais , Linhagem Celular , Humanos , Camundongos , Monócitos/virologia , Células Tumorais Cultivadas , ÁguaRESUMO
Smoking is associated with an increased risk of respiratory tract infection in adults. In children, exposure to cigarette smoke is a risk factor for respiratory tract infection and bacterial meningitis: Active smoking and passive exposure to cigarette smoke is also associated with carriage of some potentially pathogenic species of bacteria in both adults and children. The aims of the study were to determine the effect of active smoking on: (1) bacterial binding to epithelial cells; (2) expression of host cell antigens that act as receptors for some species; and (3) the effects of passive exposure to water-soluble components of cigarette smoke on bacterial binding. Flow cytometry was used to assess binding to buccal epithelial cells of the following species labelled with fluorescein isothiocyanate: Neisseria meningitidis, Neisseria lactamica, Streptococcus pneumoniae, Bordetella pertussis, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus. Flow cytometry was also used to assess expression of host cell antigens which have been identified as bacterial receptors. For each species, binding to cells of smokers was significantly higher than to cells of non-smokers; however, expression of host cell antigens was similar on epithelial cells of both groups. Non-dilute cigarette smoke extract reduced binding of bacteria to epithelial cells, but dilutions between 1 in 10 and 1 in 320 enhanced binding. We conclude that smokers might be more densely colonised by a variety of potentially pathogenic bacteria. The enhanced bacterial binding to epithelial cells of smokers is not related to enhanced expression of host cell antigens that can act as receptors for some species, but possibly to components in the smoke that alter charge or other properties of the epithelial cell surface. Passive coating of mucosal surfaces with components of cigarette smoke might enhance binding of potentially pathogenic bacteria.
Assuntos
Aderência Bacteriana , Células Epiteliais/microbiologia , Bactérias Gram-Negativas/fisiologia , Cocos Gram-Positivos/fisiologia , Mucosa Bucal/microbiologia , Lectinas de Plantas , Fumar , Adulto , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Superfície/análise , Citometria de Fluxo , Bactérias Gram-Negativas/isolamento & purificação , Cocos Gram-Positivos/isolamento & purificação , Humanos , Lactente , Lectinas/metabolismo , Camundongos , Mucosa Bucal/citologiaRESUMO
Asymptomatic infection due to Bordetella pertussis has been suggested to be one cause of sudden infant death syndrome (SIDS). We examined developmental and environmental factors previously found to affect binding of another toxigenic species, Staphylococcus aureus, to human epithelial cells: expression of the Lewis(a) antigen; infection with respiratory syncytial virus (RSV); exposure to cigarette smoke; and the inhibitory effect of breast milk on bacterial binding. Binding of two strains of B. pertussis (8002 and 250825) to buccal epithelial cells was significantly reduced by treating the cells with monoclonal antibodies to Lewis(a) (P < 0.05) and Lewis(x) (P < 0.01) antigens. Both strains bound in significantly greater numbers to cells from smokers compared with cells from non-smokers (P < 0.05). HEp-2 cells infected with RSV subtypes A or B had higher binding indices for both 8002 (P < 0.001) and 250825 (P < 0.01). On RSV-infected cells, there was significantly enhanced binding of monoclonal antibodies to Lewis(x) (P < 0.05), CD14 (P < 0.001) and CD18 (P < 0.01); and pre-treatment of cells with anti-CD14 or CD18 also significantly reduced binding of both strains of B. pertussis. Pre-treatment of the bacteria with human milk significantly reduced their binding to epithelial cells. The results are discussed in relation to our three-year survey of bacterial carriage among 253 healthy infants, their mothers and local SIDS cases between 1993-1995 and in relation to the change to an earlier immunisation schedule for infants and the recent decline in SIDS in Britain.
Assuntos
Aderência Bacteriana , Bordetella pertussis/patogenicidade , Morte Súbita do Lactente/etiologia , Anticorpos Monoclonais/imunologia , Bactérias/isolamento & purificação , Antígenos CD18/imunologia , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Células Cultivadas , Epitélio/microbiologia , Humanos , Lactente , Recém-Nascido , Antígenos do Grupo Sanguíneo de Lewis/biossíntese , Antígenos do Grupo Sanguíneo de Lewis/imunologia , Receptores de Lipopolissacarídeos/imunologia , Leite Humano/imunologia , Infecções por Vírus Respiratório Sincicial/complicações , Estudos Retrospectivos , Fumar/efeitos adversos , Morte Súbita do Lactente/epidemiologiaAssuntos
Adesinas Bacterianas/imunologia , Proteínas de Bactérias/imunologia , Antígenos do Grupo Sanguíneo de Lewis/imunologia , Staphylococcus aureus/imunologia , Morte Súbita do Lactente/imunologia , Distribuição por Idade , Aglutinação/imunologia , Animais , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais/imunologia , Aderência Bacteriana/imunologia , Toxinas Bacterianas/imunologia , Humanos , Imunização , Lactente , Recém-Nascido , Leite/imunologia , Nasofaringe/microbiologia , Infecções Respiratórias/imunologia , Fatores de RiscoRESUMO
Epidemiological factors associated with susceptibility to respiratory infections are similar to those associated with Sudden Infant Death Syndrome. Here we review the evidence that respiratory pathogens might be involved in some cases of Sudden Infant Death Syndrome in the context of factors identified in epidemiological studies of cot deaths: the age range affected; mother' smoking; respiratory viral infections; immunisation status. Both laboratory and epidemiological evidence suggests that vulnerability of infants to infectious agents depends on interactions between genetic, developmental and environmental factors that contribute to colonisation by microorganisms, the inflammatory and specific immune responses and the infants' physiological responses to inflammatory mediators. A model is proposed to explain how microorganisms might trigger a series of events resulting in some of these unexpected deaths and discusses how the the present recommendations regarding child care practices might help reduce the numbers of Sudden Infant Death Syndrome cases associated with infectious agents.
Assuntos
Infecções Bacterianas/complicações , Morte Súbita do Lactente/etiologia , Viroses/complicações , Toxinas Bacterianas/toxicidade , Humanos , Imunização , Lactente , Recém-Nascido , Fumar/efeitos adversos , Morte Súbita do Lactente/prevenção & controleRESUMO
There is evidence that the Lewis(a) blood group antigen is one of the receptors for a number of potentially pathogenic microorganisms. To determine how widely distributed the microbial adhesins are that bind this antigen, anti-idiotypic antibodies produced against monoclonal anti-Lewis(a) were used in coagglutination assays to screen a variety of species. The following were agglutinated: 7/7 strains of Staphylococcus aureus; 10/19 (53%) strains of Neisseria meningitidis; 8/13 (62%) strains of Haemophilus influenzae; 1/3 strains of Helicobacter pylori; 1/2 strains of Neisseria gonorrhoeae; 1/2 strains of Candida albicans. The application of the anti-idiotypic antibodies to studies of host cell receptors, isolation of adhesins and development of new epidemiological typing reagents is discussed.
Assuntos
Adesinas Bacterianas/imunologia , Anticorpos Anti-Idiotípicos/biossíntese , Antígenos do Grupo Sanguíneo de Lewis/imunologia , Testes de Aglutinação , Animais , Sítios de Ligação de Anticorpos , Ensaio de Imunoadsorção Enzimática , Feminino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
A 67 kDa protein was isolated from cell membrane preparations of Staphylococcus aureus (NCTC 10655) by affinity adsorption with synthetic Lewis a antigen conjugated to Synsorb beads. Pre-treatment of buccal epithelial cells expressing Lewis a with the purified protein reduced binding of the staphylococcal strain to a greater extent than the material not bound to the Synsorb beads. The significance of this work is discussed with reference to expression of Lewis a antigen in infants and the proposed role of toxigenic strains of staphylococci in some cases of sudden infant death syndrome.
Assuntos
Adesinas Bacterianas , Aderência Bacteriana/imunologia , Aderência Bacteriana/fisiologia , Antígenos do Grupo Sanguíneo de Lewis/metabolismo , Staphylococcus aureus/imunologia , Ligação Competitiva , Parede Celular/química , Bochecha , Cromatografia de Afinidade , Eletroforese em Gel de Poliacrilamida , Humanos , Lactente , Mucosa Bucal/citologia , Morte Súbita do Lactente/etiologiaRESUMO
Toxigenic bacteria such as Bordetella pertussis and Staphylococcus aureus have been implicated in some cases of sudden infant death syndrome (SIDS). We have previously demonstrated that the Lewis(a) antigen is an epithelial cell receptor for S. aureus, and this study demonstrated that Lewis(a) on human monocytes is also a receptor for staphylococcal enterotoxin B (SEB). Values obtained in assays for production of TNF-alpha and nitric oxide were greater for monocytes treated with SEB compared with those treated with lipopolysaccharide (LPS). Exposure to LPS increased the expression of Lewis(a) on monocytes. These results are discussed with reference to the reported enhancement of endotoxic shock by pyrogenic toxins.
Assuntos
Anticorpos Monoclonais/farmacologia , Enterotoxinas/metabolismo , Antígenos CD15/metabolismo , Monócitos/imunologia , Sítios de Ligação , Enterotoxinas/farmacologia , Humanos , Monócitos/metabolismo , Óxido Nítrico/metabolismo , Staphylococcus aureus , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Sudden Unexpected Nocturnal Deaths (SUND) occur in young, apparently healthy immigrant workers from Thailand, the Philippines and Bangladesh living among ex-patriot labour forces in countries such as Singapore and Saudi Arabia. Several factors associated with these deaths are similar to those observed for Sudden Infant Death Syndrome (SIDS): sleep related and mainly nocturnal occurrence; no prodromal illnesses other than mild respiratory tract infection; exposure to cigarette smoke; absence of invasive microorganisms at autopsy. The hypotheses proposed to explain these deaths in adults are examined. Based on our studies of the role toxigenic bacteria might play in some cases of SIDS, we suggest a new approach to the investigation of SUND.