Hintergrund: Wird bei Früh- und Neugeborenen (FG/NG) aufgrund klinischer Symptome das Vorliegen einer Sepsis vermutet, werden zur Sicherung der Diagnose Laborparameter wie C-reaktives Protein (CrP), Interleukin 6 (IL 6) und in jüngerer Zeit Procalcitonin (PCT) bestimmt.

ABSTRACT In pneumococcal meningitis it is assumed that bacteria cross the blood-brain barrier (BBB), which consists mainly of cerebral endothelial cells. The effect of Streptococcus pneumoniae on the BBB was investigated with an in vitro BBB model using a human brain microvascular endothelial cell line (HBMEC) and primary cultures of bovine brain microvascular endothelial cells (BBMEC). Within a few hours of incubation with pneumococci, rounding and detachment of the HBMEC were observed, and the transendothelial electrical resistance of the BBMEC monolayer decreased markedly. An S. pneumoniae mutant deficient in pneumolysin did not affect the integrity of the endothelial cell monolayer. Neither cell wall fragments nor isolated pneumococcal cell walls induced changes of endothelial cell morphology. However, purified pneumolysin caused endothelial cell damage comparable to that caused by the viable pneumococci. The cell detachment was dependent on de novo protein synthesis and required the activities of caspase and tyrosine kinases. The results show that pneumolysin is an important component for damaging the BBB and may contribute to the entry of pneumococci into the cerebral compartment and to the development of brain edema in pneumococcal meningitis.

Apoptosis followed by macrophage phagocytosis is the principal mechanism by which neutrophil granulocytes (PMN) are removed from the site of inflammation. To investigate whether Streptococcus pneumoniae causes apoptosis of PMN, we exposed PMN to viable and heat-killed pneumococci and purified pneumococcal cell walls (PCW). The occurrence of PMN cell death was quantified by flow cytometry using annexin V/propidium iodide labelling of the cells. Intracellular histone-associated DNA fragments were quantified by ELISA. The presence of apoptosis was confirmed by in situ tailing. Exposure of PMN to viable pneumococci caused necrosis of the cells. The pneumococcal cytotoxin pneumolysin, the bacterial production of hydrogen peroxide, and PCW contributed to necrosis. Heat-killed pneumococci accelerated the process of apoptosis observed in cultivated non-stimulated PMN in vitro. These results demonstrated that pneumococci induce PMN cell death. Depending on the intensity of the stimulus, PMN necrosis and apoptosis were observed.