GRANULOCYTES IN THE SUBARACHNOID SPACE OF HUMANS AND RABBITS WITH BACTERIAL-MENINGITIS UNDERGO APOPTOSIS AND ARE ELIMINATED BY MACROPHAGES

The contribution of leukocyte apoptosis to the resolution of meningeal inflammation in bacterial meningitis was studied in the cerebrospinal fluid (CSF) and in meningeal infiltrates of humans and rabbits by in situ tailing, flow cytometry, agarose gel electrophoresis, and electro n microscopy. In humans, the rate of apoptotic granulocytes was 21.0 /- 20.8% (n = 11) in cytocentrifuge preparations and 3.3 +/- 3.4 (n = 14) in putride infiltrates of autopsy cases (P = 0.02). In rabbits, CS F pleocytosis peaked 8 h after the initiation of antibiotic treatment (5311 +/- 3122/mu l). At this time, the rate of apoptotic granulocytes was 15.2 +/- 7.3% in CSF and 1.8 +/- 1.4% in the meningeal infiltrate s (each group n = 6, P = 0.007). Thereafter, the rate of apoptotic gra nulocytes in CSF declined below 10%. In humans and rabbits, bands repr esenting internucleosomal fragments of approximately 180 base pairs an d multiples thereof were documented on agarose gels. Phagocytosis of a poptotic granulocytes by macrophages was visualized by light and elect ron microscopy. In conclusion, during resolution of subarachnoid space inflammation in bacterial meningitis, a substantial fraction of granu locytes undergoes apoptosis. These granulocytes are removed by phagocy tosis by macrophages. Apoptosis is more frequent in granulocytes float ing in the CSF than in adherent cells.