Complement (C5)-derived chemotactic activity accounts for accumulation of polymorphonuclear leukocytes in cerebrospinal fluid of rabbits with pneumococcal meningitis

Abstract

Experiments were performed to identify the chemoattractant for polymorphonuclear leukocytes that appears in the CSF of rabbits with experimental pneumococcal meningitis. Meningitis was induced in anesthetized New Zealand white rabbits by injecting 104 cells of stationary-phase Streptococcus pneumoniae type III intracisternally. Before bacteria were injected, CSF contained neither polymorphonuclear leukocytes nor chemotactic activity. Significant chemotactic activity for rabbit polymorphonuclear leukocytes was detected 12 h after inoculation with bacteria and was maximal after 18-20 h. Chemotactic activity appeared in CSF while concentrations of pneumococci and total protein were increasing but before there was any accumulation of polymorphonuclear leukocytes. The chemotactic activity in CSF was heat stable (56.degree. C for 30 min), eluted from Sephadex G-75 with a profile identical to that of the chemotactic activity in zymosan-activated rabbit serum and was inhibited by treatment with antibodies to native human complement C5. Preincubation of polymorphonuclear leukocytes with partially purified rabbit C5a selectively inhibited their subsequent chemotactic responses by CSF. Evidently, complement (C5)-derived chemotactic activity appears in CSF during the course of experimental pneumococcal meningitis in rabbits and suggest that this activity accounts for the accumulation of polymorphonuclear leukocytes observed in this infection.