Several carcinoembryonic antigens (CD66) serve as receptors for gonococcal opacity proteins - PubMed (original) (raw)
Several carcinoembryonic antigens (CD66) serve as receptors for gonococcal opacity proteins
T Chen et al. J Exp Med. 1997.
Abstract
Neisseria gonorrhoeae (GC) is a human pathogen that adheres to and invades genital surfaces. Although pili are required for the initial adherence, the interaction of GC with epithelial cells is also promoted by a family of outer membrane proteins, the opacity (Opa) proteins such as OpaA protein from strain MS11. Studies have demonstrated that the interaction of the OpaA GC with epithelial cells involves binding to heparan sulfate attached to syndecan receptors. However, other Opa proteins interact with CEA gene family member 1 (CGM1) or biliary glycoprotein (BGP), members of the CD66 antigen family. In this study, we demonstrate that, in addition, the 180-kD carcinoembryonic antigen (CEA) is a receptor for Opa proteins. This conclusion was based on the following observations. First, transfected HeLa cells expressing CEA (HeLa-CEA) and the CEA-expressing colon cancer cell line (LS 174T) bound and subsequently engulfed the Opa+ bacteria. These interactions were inhibited by anti-CEA antibody, but could not be inhibited by addition of heparin. Furthermore, OpaI E. coli directly bound purified CEA. We also compared the adherence and invasion by Opa+ bacteria of CD66 transfected HeLa cells: HeLa-BGPa, HeLa-CGM6, HeLa-NCA, HeLa-CGM1a, HeLa-CEA, and HeLa-Neo serving as negative control. Using OpaI as the prototype, the relative ability of the transfected HeLa cell lines to support adherence was (CEA = BGPa >CGM1a >NCA >>CGM6 = Neo). The ability to mediate invasion of the transfectant cells was (CGM1a >CEA >BGPa >NCA >CGM6 = Neo). Among the Opa proteins tested, OpaC proved to be bifunctional, able to mediate adherence to both syndecan receptors and to CD66 antigens.
Figures
Figure 1
Adherence and internalization of pEXI by HeLa cells transfected with various CD66 antigens. All the cell lines were grown to confluence in 24well culture plates containing RPMI medium 1640 and were incubated with pEXI for 4.5 h. The adherent and intracellular E. coli were distinguished by incubation with gentamicin. (A) The ability of these cell lines to bind pEXI: HeLa-CEA >HeLaBGP >HeLa-CGM1a >NCA >>HeLa-CGM6 = HeLa-Neo = 0. (B) The number of intracellular bacteria. Although HeLaCGM1a showed the highest internalization of pEXI, HeLaCEA could also engulf pEXI. The internalization of pEXI into HeLaBGP was negligible. Bars, SEM.
Figure 2
Electron micrographs of internalization of OpaI E. coli and GC by HeLa-CEA and LS 174T. The micrographs demonstrate the ability of HeLa-CEA to internalize OpaI E. coli (A) and OpaI GC (B). CEAexpressing colon cancer cells (LS 174T) were also able to engulf OpaI E. coli (C) and OpaI GC (D). The engulfment of OpaI CG by HeLaCGM1a (E) served as a positive control. Bar, 1 μm.
Figure 3
The binding of purified CEA to pEXI. Equal numbers of pGEM (Opa−) and pEXI (OpaI) were suspended in RPMI containing equal amounts of CEA. After incubation, the bacteria were recovered by centrifugation, washed, and lysed, and the lysates were subjected to SDS-PAGE and transfered to Immobilon-P membrane. The CEA bound on the bacteria was detected by anti-CD66 mAb (COL-1). Much more CEA was bound by pEXI than by pGEM.
Figure 4
Multiple Opa proteins promote adherence to HeLa-CEA. pGEM, pEXA, pEXB, pEXC, pEXH, and pEXI were incubated with HeLaCEA (A) for 4 h. All of Opa+ E. coli adhered to the cell lines. (B) Addition of COL-1 antibody (CD66) inhibited adherence of OpaI and OpaC E. coli to HeLaCEA. Control antibody IB4 (CD18) had no effect when added at the same final concentration (25 μg/ml). The interaction of pEXI and pEXC with HeLa-CEA was for 2 h and only accounted for the lower bacterial counts.
Figure 4
Multiple Opa proteins promote adherence to HeLa-CEA. pGEM, pEXA, pEXB, pEXC, pEXH, and pEXI were incubated with HeLaCEA (A) for 4 h. All of Opa+ E. coli adhered to the cell lines. (B) Addition of COL-1 antibody (CD66) inhibited adherence of OpaI and OpaC E. coli to HeLaCEA. Control antibody IB4 (CD18) had no effect when added at the same final concentration (25 μg/ml). The interaction of pEXI and pEXC with HeLa-CEA was for 2 h and only accounted for the lower bacterial counts.
Figure 5
The interaction of Opa+ GC with HeLa-CEA cells and CEA-expressing colon cancer cells LS 174T. Opa+ GC were incubated with HeLaCEA (A) in RPMI medium 1640 buffer with or without soluble heparin (30 μg/ml). OpaA and OpaI promoted adherence to HeLa-CEA, and OpaA-mediated adherence was inhibited by heparin. Similar results were observed with CEA-expressing colon cancer line LS 174T.
Figure 5
The interaction of Opa+ GC with HeLa-CEA cells and CEA-expressing colon cancer cells LS 174T. Opa+ GC were incubated with HeLaCEA (A) in RPMI medium 1640 buffer with or without soluble heparin (30 μg/ml). OpaA and OpaI promoted adherence to HeLa-CEA, and OpaA-mediated adherence was inhibited by heparin. Similar results were observed with CEA-expressing colon cancer line LS 174T.
Figure 6
Binding specificity of OpaC bacteria for both heparan sulfate and CD66 receptors. OpaC GC were incubated with wild-type CHO-K1 cells and the isogenic mutants 745 and 677 lacking surface heparan sulfate. OpaC GC adhered to CHO-K1 cells, but not the 745 and 677 mutants (A). (B) pGEM, pEXA, and pEXC were incubated with HeLa-CGM1a cells in RPMI 1640 medium for 4.5 h. The adherent and intracellular E. coli were distinguished by incubation with gentamicin. Only pEXC was recovered in large numbers after gentamicin treatment, although both pEXA and pEXC adhered to the HeLa-CGM1a.
Figure 6
Binding specificity of OpaC bacteria for both heparan sulfate and CD66 receptors. OpaC GC were incubated with wild-type CHO-K1 cells and the isogenic mutants 745 and 677 lacking surface heparan sulfate. OpaC GC adhered to CHO-K1 cells, but not the 745 and 677 mutants (A). (B) pGEM, pEXA, and pEXC were incubated with HeLa-CGM1a cells in RPMI 1640 medium for 4.5 h. The adherent and intracellular E. coli were distinguished by incubation with gentamicin. Only pEXC was recovered in large numbers after gentamicin treatment, although both pEXA and pEXC adhered to the HeLa-CGM1a.
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