Inhibition of bacterial motility with human antiflagellar monoclonal antibodies attenuates Pseudomonas aeruginosa-induced pneumonia in the immunocompetent rat.
Two human monoclonal antibodies, directed against the type a and type b flagellar proteins of Pseudomonas aeruginosa, inhibited bacterial motility in vitro specifically and in a concentration-dependent manner. In order to determine if this decreased bacterial motility was associated with a decreased pathogenicity, the ability of these human antiflagellar monoclonal antibodies to attenuate P. aeruginosa-induced pneumonia in the rat was assessed. Incubation of P. aeruginosa with a 1:1 mixture of the human antiflagellar monoclonal antibodies prior to pulmonary instillation significantly (P < 0.05) ameliorated the bacterium-induced decrease in arterial blood oxygen pressure, blunted the increase in respiratory rate, and markedly reduced the area of pulmonary inflammation. Similarly, intravenous administration of the human antiflagellar monoclonal antibodies 1 h after pulmonary instillation of the bacteria also reduced the in vivo pathogenicity of P. aeruginosa. Therefore, human antiflagellar monoclonal antibodies can decrease the in vitro motility of P. aeruginosa and can reduce its in vivo pathogenicity when administered either before or after bacterial challenge.
Landsperger
W J
WJ
Immunotherapy Division, Baxter Healthcare Corporation, Duarte, California.
Kelly-Wintenberg
K D
KD
Montie
T C
TC
Knight
L S
LS
Hansen
M B
MB
Huntenburg
C C
CC
Schneidkraut
M J
MJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology; D005407:Flagella / Q000276:immunology*; D007167:Immunotherapy; D008297:Male; D011014:Pneumonia / Q000628:therapy*; D011552:Pseudomonas Infections / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial