Mediation of the killing of rough, mucoid isolates of Pseudomonas aeruginosa from patients with cystic fibrosis by the alternative pathway of complement

The mechanism of killing of 12 serum-sensitive strains of mucoid Pseudomonas aeru-ginosa isolated from patients with cystic fibrosis was investigated. A quantitative assay indicated that more than 900/0 of cells were killed in 500/0 normal human serum (NHS). All strains failed to grow in NHS concentrations of>100/0. Killing was unaffected by adsorption of NHS with the mucoid bacteria or chelation with MgCl2-ethyleneglycol bis(f3-aminoethyl ether)~N'-tetraacetate (MgClrEGTA) but was abolished in serum heated to 50 C for 20 min. Incubation of NHS with mucoid P. aeruginosa reduced the hemolytic capability of MgCI2-EGTA-chelated NHS against rabbit red blood cells by 560/0-990/0. Killing of the serum-sensitive mucoid strains was also seen in hypogamma-globulinemic serum. These data suggest that killing of such strains by NHS can occur via antibody-independent activation of the alternative pathway of complement. The im-portance of this finding lies in the implication that complement levels in the lungs of patients with cystic fibrosis who are colonized by these organisms are inadequate to deal with this chronic, progressive infection. The inability of patients with cystic fibrosis (CF