title: Very late antigen-5 and complement receptor type 3 cooperatively mediate the interaction between Bordetella pertussis and human monocytes.
abstract: Nonopsonized Bordetella pertussis, the causative agent of whooping cough, can attach to and become ingested by human monocytes. It has been reported that complement receptor type 3 (CR3) on human monocyte-derived macrophages binds filamentous hemagglutinin expressed on B. pertussis. In the present study, the role of very late antigen-5 (VLA-5) in the attachment of B. pertussis to adherent human monocytes was investigated. It was found that soluble fibronectin and soluble mAb against VLA-5 markedly inhibited the attachment of B. pertussis to monocytes. When VLA-5 on monocytes was cross-linked by plating these cells onto surfaces precoated with fibronectin or mAb against VLA-5, the binding of both B. pertussis and C3bi-coated sheep erythrocytes to these cells was significantly enhanced, whereas the binding of a B. pertussis mutant strain deficient in filamentous hemagglutinin was not affected. The enhanced attachment of B. pertussis to monocytes plated onto fibronectin-coated surfaces was markedly inhibited by soluble mAb against CR3. Neutrophils, which express similar levels of CR3 and about 10-fold lower levels of VLA-5 as compared with monocytes, did not bind B. pertussis. Together, these results indicate that VLA-5 is involved in the attachment of B. pertussis to monocytes and that cross-linking of VLA-5 enhances the attachment of B. pertussis to monocytes by augmenting the binding activity of CR3. We propose that the attachment of B. pertussis to monocytes occurs in two steps: binding and cross-linking of VLA-5 by B. pertussis enhances the binding activity of CR3, which in turn facilitates the subsequent binding of these bacteria to the latter receptor.
authors.affiliation: Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
authors.forename: W L
authors.initials: WL
authors.lastname: Hazenbos
authors.forename: B M
authors.initials: BM
authors.lastname: van den Berg
authors.forename: R
authors.initials: R
authors.lastname: van Furth
mesh_terms: D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001422:Bacterial Adhesion; D001886:Bordetella pertussis / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology; D006388:Hemagglutinins / Q000502:physiology; D006801:Humans; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000382:microbiology*; D017469:Receptors, Fibronectin / Q000502:physiology*; D010566:Virulence Factors, Bordetella
chemical_list: D018829:Adhesins, Bacterial; D000911:Antibodies, Monoclonal; D005353:Fibronectins; D006388:Hemagglutinins; D016177:Macrophage-1 Antigen; D017469:Receptors, Fibronectin; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis