Influence of granulocytes on brain edema, intracranial pressure, and cerebrospinal fluid concentrations of lactate and protein in experimental meningitis

Brain water content (brain edema), intracranial pressure, and cerebrospinal fluid (CSF) concentrations of lactate and protein increased significantly during 24 h of experimental meningitis due to Streptococcus pneumoniae, but changes were similar in normal and neutropenic rabbits. In sterile meningitis induced by N-formyl-methionyl-leucyl-phenyl-alanine (fMLP), low and high doses of fMLP were equally effective in inducing CSF pleocytosis, whereas only high doses of fMLP caused brain edema. High doses of fMLP injected intracisternally during pneumococcal meningitis also increased brain water content. The fMLP did not significantly increase intracranial pressure or CSF concentrations of lactate or protein in sterile or pneumococcal meningitis, nor did it cause brain edema in neutropenic animals. Thus, granulocytes may contribute to brain edema during meningitis if adequately stimulated, but intracranial pressure and CSF protein and lactate concentrations appear independent of granulocytes. Stimulation does not appear to occur early in meningitis, when granulocytes were without effect on brain edema.

Activation of cyclic AMP response element-binding protein (CREB) in aggressive periodontal disease

OBJECTIVES: To report a novel observation of neutrophil signal transduction abnormalities in patients with localized aggressive periodontitis (LAP) that are associated with an enhanced phosphorylation of the nuclear signal transduction protein cyclic AMP response element-binding factor (CREB). METHOD AND MATERIALS: Peripheral venous blood neutrophils of 18 subjects, 9 patients with LAP and 9 race-, sex-, and age-matched healthy controls, were isolated and prepared using the Ficoll-Hypaque density-gradient technique. Neutrophils (5.4 x 10(6)/mL) were stimulated with the chemoattractant FMLP (10(-6) mol/L) for 5 minutes and lysed. Aliquots of these samples were separated by SDS-PAGE (60 microg/lane) on 9.0% (w/v) polyacrylamide slab gels and transferred electrophoretically to polyvinyl difluoride membranes. The cell lysates were immunoblotted with a 1:1,000 dilution of rabbit-phospho-CREB antibody that recognizes only the phosphorylated form of CREB at Ser133. The activated CREB was visualized with a luminol-enhanced chemoluminescence detection system and evaluated by laser densitometry. RESULTS: In patients with LAP, the average activation of CREB displayed an overexpression for the unstimulated peripheral blood neutrophils of 80.3% (17.5-fold) compared to healthy controls (4.6%). CONCLUSION: LAP neutrophils who express their phenotype appear to be constitutively primed, as evidenced by activated CREB in resting cells compared to normal individuals. The genetically primed neutrophil phenotype may contribute to neutrophil-mediated tissue damage in the pathogenesis of LAP.