Bispecific antibodies overcome the opsonin-receptor mismatch of cystic fibrosis in vitro: restoration of neutrophil-mediated phagocytosis and killing of Pseudomonas aeruginosa. J Immunol 1997 Apr 01;158(7):3474-82
Date
04/01/1997Pubmed ID
9120309Scopus ID
2-s2.0-0031114044 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Inflammation and infection associated with bacterial pathogens, primarily Pseudomonas aeruginosa (Pa), are the primary causes of morbidity and mortality for cystic fibrosis (CF) patients. CF patients may be predisposed to these bacterial infections by a defect in phagocytosis due to "opsonin-receptor mismatch," in which a complement receptor (CR1) and an important opsonin (iC3b) are destroyed by proteolytic enzymes. We show that opsonin-receptor mismatch can be mitigated in vitro using a bispecific Ab (bsAb) to cross-link neutrophils via the beta-chain of leukocyte integrins (CD18) to bacterial epitopes or C3d on opsonized Pa. Two chemically cross-linked bsAb were constructed with mAb specific for C3d (or the O-specific side chain of Fisher Devlin Immunotype 1 Pa) and CD18. Using an in vitro model of elastase-mediated opsonin-receptor mismatch, these bsAb specifically enhanced Pa phagocytosis and killing, with the anti-C3d-containing bsAb restoring the levels of phagocytosis to approximately those for the non-elastase-treated opsonic control. These results encourage the further investigation of bsAb as therapeutic agents for bacterial infection in the lungs of CF patients.
Author List
McCormick LL, Karulin AY, Schreiber JR, Greenspan NSMESH terms used to index this publication - Major topics in bold
Antibodies, BispecificAntibody Specificity
CD18 Antigens
Cell Separation
Cells, Cultured
Complement System Proteins
Cystic Fibrosis
Flow Cytometry
Humans
Neutrophils
Opsonin Proteins
Phagocytosis
Protein Binding
Pseudomonas Infections
Pseudomonas aeruginosa
Receptors, Immunologic
