RESUMO
The case of an infant with multiple, rapidly progressive, soft-tissue infections is presented. Despite features suggesting a neutrophil disorder, results of screening tests of phagocyte function were normal. A novel, multifaceted leukocyte disorder-distinguished by defects in shape change, chemotaxis, ingestion, degranulation, superoxide anion production, and bactericidal activity-was established secondary to a defect in Rac2.
Assuntos
Neutrófilos/fisiologia , Infecções dos Tecidos Moles/genética , Proteínas rac de Ligação ao GTP/genética , Atividade Bactericida do Sangue , Quimiotaxia de Leucócito , Humanos , Recém-Nascido , Masculino , Fagocitose , Transdução de Sinais , Infecções dos Tecidos Moles/imunologia , Superóxidos/metabolismo , Proteína RAC2 de Ligação ao GTPRESUMO
BACKGROUND: Bacterial translocation is a process believed to result in nosocomial infections. Secretory IgA (sIgA) may have a role in the prevention of translocation by its ability to bind and aggregate bacteria, a function termed "immune exclusion." The present study was done to determine the effect of specific binding of sIgA to bacteria on the movement of these organisms across the intact epithelial membrane. STUDY DESIGN: Bacterial translocation across intact intestinal segments of rats were assessed in vitro using the Ussing model. Secretory IgA (0.25 mg per mL) from pooled human colostrum was added to the perfused segments of ileum in the Ussing system. Subsequently, the membranes were exposed to 5 x 10(9) cfu per mL Escherichia coli on their mucosal side. A second experiment tested the effect of human IgG when perfused with E. coli using the same preparation. All experiments had paired matched rats in a control group without immunoglobulin. The ability of sIgA and IgG to bind to E. coli was studied by an in vitro assay, as well as by transmission electron microscopy and immunofluorescence of random IgA/E. coli experiments. Measurements obtained in all experimental and control groups were the incidence and amount of bacterial passage and the potential difference generated by the intestinal segments (an index of viability). RESULTS: There were no differences in potential difference between control and experimental groups in either of the two experiments. Secretory IgA bound E. coli and completely prevented passage of E. coli as compared with rats in the control group. IgG bound E. coli; however, the incidence of passage was equal to that of rats in the control group. However, the presence of IgG resulted in a significantly reduced number of bacteria that passed when compared with controls (p < 0.05). Electron microscopic studies revealed intact surface morphology and immunofluorescence revealed aggregates of IgA and E. coli on the mucosal, but not submucosal, surface of the ileal membranes. CONCLUSIONS: This study provides direct evidence of immune exclusion by sIgA. When bound to bacteria, it prevents passage across a morphologically intact segment of viable intestinal tissue.
Assuntos
Escherichia coli/imunologia , Imunoglobulina A Secretora/fisiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Animais , Imunofluorescência , Íleo/citologia , Íleo/imunologia , Íleo/microbiologia , Técnicas In Vitro , Masculino , Microscopia Eletrônica , Ratos , Ratos Sprague-DawleyRESUMO
Catheter sepsis with catheter removal is an important problem in patients with short-bowel syndrome. We determined the incidence of catheter sepsis and the catheter salvage rate in 20 pediatric patients with short-bowel syndrome. To evaluate the intestine as a source and translocation as the pathophysiologic mechanism for catheter sepsis, we identified the sepsis organisms, compared them with the fecal flora, and used mesenteric lymph node cultures to document translocation. The incidence of catheter sepsis was significantly higher in patients with short-bowel syndrome than in patients without short-bowel syndrome (7.8 vs 1.3 per 1000 catheter days). Overall catheter salvage was 42% and was highest in gram-negative sepsis (71%). Enteric organisms were responsible for 62% of cases of catheter sepsis in patients with short-bowel syndrome vs 12% in patients without short-bowel syndrome. Anaerobes were strikingly absent in 25 of 28 stool cultures. The sepsis organism was identified in the fecal flora in 19 of 28 cases. The dominant fecal organism or yeast was the septic organism in 12 of these 19 cases and was isolated in three of four mesenteric lymph node cultures. Our findings support translocation as a mechanism in catheter sepsis in patients with short-bowel syndrome.