An iron-binding protein common to many external secretions

Masson, Pierre; Heremans, J. F.; Dive, C

doi:10.1016/0009-8981(66)90004-0

Cited by 560 publications

(269 citation statements)

References 9 publications

Supporting

Mentioning

263

Contrasting

Unclassified

Order By: Relevance

“…As Lf was recently shown to facilitate attachment of Ad5 to epithelial cells by serving as a bridge between the virus and the target cell surface (Johansson et al, 2007), we investigated the effect of Lf on infection of APCs. Lf is present in mucosal tissues and in most bodily fluids, such as milk, tear fluid, saliva, nasal secretions and vaginal mucus, and at low concentration in serum (Masson et al, 1966;Weinberg, 2001). Lf is of interest with regard to DCs as it can interact directly with these cells and modulate important functions such as migration, cell activation and induction of T-cell responses (de la Rosa et al, 2008;Puddu et al, 2009;Spadaro et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus–adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN

Adams

Bond

Havenga

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

The coxsackievirus-adenovirus receptor (CAR) is the described primary receptor for adenovirus serotype 5 (Ad5), a common human pathogen that has been exploited as a viral vector for gene therapy and vaccination. This study showed that monocytes and dendritic cells (DCs), such as freshly isolated human blood myeloid DCs, plasmacytoid DCs and monocyte-derived DCs, are susceptible to recombinant Ad5 (rAd5) infection despite their lack of CAR expression. Langerhans cells and dermal DCs from skin expressed CAR, but blocking CAR only partly decreased rAd5 infection, together suggesting that other receptor pathways mediate viral entry of these cells. Lactoferrin (Lf), an abundant protein in many bodily fluids known for its antiviral and antibacterial properties, promoted rAd5 infection in all cell populations except plasmacytoid DCs using a CAR-independent process. Lf caused phenotypic differentiation of the DCs, but cell activation played only a minor role in the increase in infection frequencies. The C-type lectin receptor DC-SIGN facilitated viral entry of rAd5-Lf complexes and this was dependent on highmannose-type N-linked glycans on Lf. These results suggest that Lf present at high levels at mucosal sites can facilitate rAd5 attachment and enhance infection of DCs. A better understanding of the tropism and receptor mechanisms of Ad5 may help explain Ad5 pathogenesis and guide the engineering of improved rAd vectors. INTRODUCTIONAdenoviruses are frequent causes of acute upper respiratory tract infections and can be responsible for ocular and gastrointestinal illnesses in humans. They have also been exploited for the development of replication-incompetent viral vectors because their genomes allow large inserts of expression cassettes, thereby offering efficient gene delivery. Recombinant adenoviruses (rAds), serotype 5 (rAd5) in particular, are commonly used vectors for gene therapy and vaccination trials (Barouch & Nabel, 2005;McConnell & Imperiale, 2004;Tatsis & Ertl, 2004). The primary receptor described for infection of most Ad species (A, C, D, E and F) is the coxsackievirus and adenovirus receptor (CAR) (Bergelson et al., 1997;Roelvink et al., 1998;Tomko et al., 1997). As currently understood, infection of Ad5 (species C) involves binding of the viral fiber knob to CAR on the target cells (Roelvink et al., 1996), followed by an interaction between the viral penton base with a v integrins on the cell surface (Wickham et al., 1993). This allows virus-receptor complexes to enter clathrin-coated pits via endocytosis Wang et al., 1998;Wickham et al., 1993). Efficient infection of Ad5 via CAR has mainly been demonstrated in vitro using immortalized cell lines with well-exposed CAR. However, CAR is naturally expressed in tight junctions between cells and therefore et al., 2007). In this study, we investigated the involvement of CAR and the influence of Lf in rAd5 infection in relevant primary human APC populations from both blood and skin. METHODSIsolation of blood DCs. This study was approved by the ethical commi...

show abstract

Section: Discussionmentioning

confidence: 99%

Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus–adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN

Adams

Bond

Havenga

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…The highest level of transferrin is in serum, and that of lactoferrin within polymorphonuclear leucocytes and in mucosal fluids (Masson et al, 1966(Masson et al, , 1969. They have protean effects on micro-organisms ; variably acting as growth factors, inducing iron uptake systems, and for selected bacteria producing bacteriostasis (Bullen, 198 1 ;Bullen et al, 1978;Griffiths, 1975;Norrod & Williams, 1978).…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin and transferrin damage of the Gram-negative outer membrane is modulated by Ca2+ and Mg2+

Ellison¹,

LaForce²,

Giehl³

et al. 1990

Journal of General Microbiology

109

View full text Add to dashboard Cite

Lactoferrin and transferrin have antimicrobial activity against selected Gram-negative bacteria, but the mechanism of action has not been defined. We studied the ability of lactoferrin and transferrin to damage the Gram-negative outer membrane. Lipopolysaccharide release by the proteins could be blocked by concurrent addition of Ca2+ and Mg2+. Addition of Ca2+ also blocked the ability of lactofenin to increase the susceptibility of Escherichia coli to rifampicin. Transferrin, but not lactoferrin, increased susceptibility of Gram-negative bacteria to deoxycholate, with reversal of sensitivity occurring with exposure to Ca2+ or Mg2+. In transmission electron microscopy studies polymyxin B caused finger-like membrane projections, but no morphological alterations were seen in cells exposed to EDTA, lactoferrin or transferrin. These data provide further evidence that lactoferrin and transferrin act as membrane-active agents with the effects modulated by Ca2+ and Mg2+.

show abstract

“…Using immunological methods, it has also been possible to demonstrate the presence of lactoferrin in various other biological fluids, as tears, saliva, nasal and bronchial secretions, gastrointestinal fluid, hepatic bile, urine, seminal fluid, and cervical mucus (18). Taken together, these findings have created the impression that lactoferrin is chiefly an epithelial secretion product.…”

mentioning

confidence: 98%

Lactoferrin, an Iron-Binbing Protein Ni Neutrophilic Leukocytes

Masson¹,

Heremans²,

Schonne³

1969

The Journal of Experimental Medicine

650

295

View full text Add to dashboard Cite

Lactoferrin, an iron-binding protein previously shown to occur in many external secretions, is identified as one of the major proteins present in human and guinea pig neutrophilic polymorphonuclear leukocytes. The identification of this protein in leukocyte extracts was based upon a comparison of its electrophoretic, antigenic, and iron-combining properties with the corresponding properties of the same protein isolated from human and guinea pig milk. Immunochemical quantitations showed that lactoferrin occurs in human neutrophilic leukocytes at the concentration of 3 µg per 106 cells. Tissue cultures from guinea pig bone marrow and spleen actively synthesized the protein, as shown both by net production of lactoferrin and incorporation of labeled amino acids into the protein. Immunohistochemical data indicate that lactoferrin first appears in myeloid cells at the stage of the promyelocyte.

show abstract

An iron-binding protein common to many external secretions

Cited by 560 publications

References 9 publications

Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus–adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN

Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus–adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN

Lactoferrin and transferrin damage of the Gram-negative outer membrane is modulated by Ca2+ and Mg2+

Lactoferrin, an Iron-Binbing Protein Ni Neutrophilic Leukocytes

Contact Info

Product

Resources

About