SUPPLEMENTAL COMPLEMENT COMPONENT C9 ENHANCES THE CAPACITY OF NEONATAL SERUM TO KILL MULTIPLE ISOLATES OF PATHOGENIC ESCHERICHIA-COLI

Previous studies demonstrated that, compared with adult serum, neonata l serum contained a diminished concentration of complement component C 9 and that supplemental C9 enhanced the capacity of neonatal serum to kill an isolate of Escherichia coli. Therefore, experiments were desig ned to determine the mechanisms by which supplemental C9 enhances the bactericidal capacity of neonatal serum and to determine whether suppl emental C9 enhances the capacity of neonatal serum to kill several dif ferent pathogenic strains of E. coli. A radiobinding assay and immunog old electron microscopy using a monoclonal anti-C9 antibody revealed t hat, compared with 40% adult serum, neonatal serum deposited a diminis hed quantity of C9 onto E. coli O7w:K1:NM. Supplemental C9 (75 mg/L) s ignificantly enhanced the quantity of C9 deposited by the neonatal ser um. Treatment with 10 mM MgEGTA (a mixture of 100 mM MgCl2 and 100 mM EGTA that blocks activation of the classic complement pathway but leav es the alternative pathway intact) abolished the capacity of neonatal serum to deposit C9 and to kill the bacteria. Supplemental C9 enhanced the capacity of neonatal serum to kill eight different blood isolates of E. coli. Therefore, supplemental C9 enhanced the capacity of neona tal serum to kill E. coli by increasing the total quantity of C9 depos ited via activation of the classic complement pathway. Neonatal serum contained sufficient quantities of classic pathway components, other t han C9, to deposit the supplemental C9 onto E. coli and to enhance bac terial killing. The bactericidal activity of neonatal serum against mu ltiple isolates of pathogenic E, coli was increased after C9 supplemen tation. We speculate that C9 deficiency may be one of the defects in a ntibacterial host defense that predisposes neonates to the acquisition of E. coli sepsis.