Lactoferrin-lipid A-lipopolysaccharide interaction: Inhibition by anti- human lactoferrin monoclonal antibody AGM 10.14

Domenico Caccavo, Antonella Afeltra, Salvatore Pece, Giuseppe Giuliani, Marina Freudenberg, Chris Galanos, Emilio Jirillo

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Lactoferrin (LF) is a glycoprotein that exerts both bacteriostatic and bactericidal activities. The interaction of LF with lipopolysaccharide (LPS) of gram-negative bacteria seems to play a crucial role in the bactericidal effect. In this study, we evaluated, by means of an enzyme-linked immunosorbent assay, the binding of biotinylated LF to the S (smooth) and R (rough) (Ra, Rb, Rc, Rd1, Rd2, and Re) forms of LPS and different lipid A preparations. In addition, the effects of two monoclonal antibodies (AGM 10.14, an immunoglobulin G1 [IgG1] antibody, and AGM 2.29, an IgG2b antibody), directed against spatially distant epitopes of human LF, on the LF-lipid A or LF-LPS interaction were evaluated. The results showed that biotinylated LF specifically binds to solid-phase lipid A, as this interaction was prevented in a dose-dependent fashion by either soluble uncoupled LF or lipid A. The binding of LF to S-form LPS was markedly weaker than that to lipid A. Moreover, the rate of LF binding to R-form LPS was inversely related to core length. The results suggest that the polysaccharide O chain as well as oligosaccharide core structures may interfere with the LF- lipid A interaction. In addition, we found that soluble lipid A also inhibited LF binding to immobilized LPS, demonstrating that, in the whole LPS structure, the lipid A region contains the major determinant recognized by LF. AGM 10.14 inhibited LF binding to lipid A and LPS in a dose-dependent fashion, indicating that this monoclonal antibody recognizes an epitope involved in the binding of LF to lipid A or some epitope in its close vicinity. In contrast, AGM 2.29, even in a molar excess, did not prevent the binding of LF to lipid A or LPS. Therefore, AGM 10.14 may represent a useful tool for neutralizing selectively the binding of LF to lipid A. In addition, the use of such a monoclonal antibody could allow better elucidation of the consequences of the LF-lipid A interaction.

Original languageEnglish
Pages (from-to)4668-4672
Number of pages5
JournalInfection and Immunity
Volume67
Issue number9
Publication statusPublished - 1999

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Lipid A
Lactoferrin
Lipopolysaccharides
Monoclonal Antibodies
Epitopes
Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Caccavo, D., Afeltra, A., Pece, S., Giuliani, G., Freudenberg, M., Galanos, C., & Jirillo, E. (1999). Lactoferrin-lipid A-lipopolysaccharide interaction: Inhibition by anti- human lactoferrin monoclonal antibody AGM 10.14. Infection and Immunity, 67(9), 4668-4672.

Lactoferrin-lipid A-lipopolysaccharide interaction : Inhibition by anti- human lactoferrin monoclonal antibody AGM 10.14. / Caccavo, Domenico; Afeltra, Antonella; Pece, Salvatore; Giuliani, Giuseppe; Freudenberg, Marina; Galanos, Chris; Jirillo, Emilio.

In: Infection and Immunity, Vol. 67, No. 9, 1999, p. 4668-4672.

Research output: Contribution to journalArticle

Caccavo, D, Afeltra, A, Pece, S, Giuliani, G, Freudenberg, M, Galanos, C & Jirillo, E 1999, 'Lactoferrin-lipid A-lipopolysaccharide interaction: Inhibition by anti- human lactoferrin monoclonal antibody AGM 10.14', Infection and Immunity, vol. 67, no. 9, pp. 4668-4672.
Caccavo, Domenico ; Afeltra, Antonella ; Pece, Salvatore ; Giuliani, Giuseppe ; Freudenberg, Marina ; Galanos, Chris ; Jirillo, Emilio. / Lactoferrin-lipid A-lipopolysaccharide interaction : Inhibition by anti- human lactoferrin monoclonal antibody AGM 10.14. In: Infection and Immunity. 1999 ; Vol. 67, No. 9. pp. 4668-4672.
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abstract = "Lactoferrin (LF) is a glycoprotein that exerts both bacteriostatic and bactericidal activities. The interaction of LF with lipopolysaccharide (LPS) of gram-negative bacteria seems to play a crucial role in the bactericidal effect. In this study, we evaluated, by means of an enzyme-linked immunosorbent assay, the binding of biotinylated LF to the S (smooth) and R (rough) (Ra, Rb, Rc, Rd1, Rd2, and Re) forms of LPS and different lipid A preparations. In addition, the effects of two monoclonal antibodies (AGM 10.14, an immunoglobulin G1 [IgG1] antibody, and AGM 2.29, an IgG2b antibody), directed against spatially distant epitopes of human LF, on the LF-lipid A or LF-LPS interaction were evaluated. The results showed that biotinylated LF specifically binds to solid-phase lipid A, as this interaction was prevented in a dose-dependent fashion by either soluble uncoupled LF or lipid A. The binding of LF to S-form LPS was markedly weaker than that to lipid A. Moreover, the rate of LF binding to R-form LPS was inversely related to core length. The results suggest that the polysaccharide O chain as well as oligosaccharide core structures may interfere with the LF- lipid A interaction. In addition, we found that soluble lipid A also inhibited LF binding to immobilized LPS, demonstrating that, in the whole LPS structure, the lipid A region contains the major determinant recognized by LF. AGM 10.14 inhibited LF binding to lipid A and LPS in a dose-dependent fashion, indicating that this monoclonal antibody recognizes an epitope involved in the binding of LF to lipid A or some epitope in its close vicinity. In contrast, AGM 2.29, even in a molar excess, did not prevent the binding of LF to lipid A or LPS. Therefore, AGM 10.14 may represent a useful tool for neutralizing selectively the binding of LF to lipid A. In addition, the use of such a monoclonal antibody could allow better elucidation of the consequences of the LF-lipid A interaction.",
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AU - Caccavo, Domenico

AU - Afeltra, Antonella

AU - Pece, Salvatore

AU - Giuliani, Giuseppe

AU - Freudenberg, Marina

AU - Galanos, Chris

AU - Jirillo, Emilio

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