The protein structure of recombinant human lactoferrin produced in the milk of transgenic cows closely matches the structure of human milk-derived lactoferrin

Thomassen, E.A.J.; Veen, Harrie A. van; Berkel, Patrick H.C. van; Nuijens, Jan H.; Abrahams, Jan Pieter

doi:10.1007/s11248-005-3233-0

Cited by 37 publications

(27 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rhLf present in the milk of transgenic animals, mice, and cows and natural hLf show very similar structural and functional properties in vitro (45,53,55). rhLf glycans may possess specific features that must be taken into account when interpreting results from in vitro and in vivo experiments (35).…”

Section: Discussionmentioning

confidence: 99%

Transgenic Cows That Produce Recombinant Human Lactoferrin in Milk Are Not Protected from Experimental Escherichia coli Intramammary Infection

et al. 2006

View full text Add to dashboard Cite

This is the first study describing an experimental mastitis model using transgenic cows expressing recombinant human lactoferrin (rhLf) in their milk. The aim of the study was to investigate the concentrations in milk and protective effects of bovine and recombinant human lactoferrin in experimental Escherichia coli mastitis. Experimental intramammary infection was induced in one udder quarter of seven first-lactating rhLf-transgenic cows and six normal cows, using an E. coli strain isolated from cows with clinical mastitis and known to be susceptible to Lf in vitro. Clinical signs were recorded during the experimental period, concentrations of human and bovine Lf and indicators of inflammation and bacterial counts were determined for milk, and concentrations of acute-phase proteins and tumor necrosis factor alpha were determined for sera and milk. Serum cortisol and blood hematological and biochemical parameters were also determined. Expression levels of rhLf in the milk of transgenic cows remained constant throughout the experiment (mean, 2.9 mg/ml). The high Lf concentrations in the milk of transgenic cows did not protect them from intramammary infection. All cows became infected and developed clinical mastitis. The rhLf-transgenic cows showed milder systemic signs and lower serum cortisol and haptoglobin concentrations than did controls. This may be explained by lipopolysaccharide-neutralizing and immunomodulatory effects of the high Lf concentrations in their milk. However, Lf does not seem to be a very efficient protein for genetic engineering to enhance the mastitis resistance of dairy cows.

show abstract

Section: Discussionmentioning

confidence: 99%

Transgenic Cows That Produce Recombinant Human Lactoferrin in Milk Are Not Protected from Experimental Escherichia coli Intramammary Infection

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The structure of the N-lobe in the truncated form is almost identical to that in the full length LF. [28][29][30] In the intact hLF, helix 11 of the N-lobe is joined by a loop to the short helix that links the two lobes. In the crystal structures of the truncated N-lobe the secondary structure at the C terminus varies depending on the stability of this region.…”

Section: Structure Of Pspa 2 In the Complex With Nlfmentioning

confidence: 99%

Structure of a Complex of Human Lactoferrin N-lobe with Pneumococcal Surface Protein A Provides Insight into Microbial Defense Mechanism

Senkovich

Cook

Mirza

et al. 2007

Journal of Molecular Biology

View full text Add to dashboard Cite

Human lactoferrin, a component of the innate immune system, kills a wide variety of microorganisms including the Gram positive bacteria Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) efficiently inhibits this bactericidal action. The crystal structure of a complex of the lactoferrin-binding domain of PspA with the N-lobe of human lactoferrin reveals direct and specific interactions between the negatively charged surface of PspA helices and the highly cationic lactoferricin moiety of lactoferrin. Binding of PspA blocks surface accessibility of this bactericidal peptide preventing it from penetrating the bacterial membrane. Results of sitedirected mutagenesis, in vitro protein binding assays and isothermal titration calorimetry measurements corroborate that the specific electrostatic interactions observed in the crystal structure represent major associations between PspA and lactoferrin. The structure provides a snapshot of the protective mechanism utilized by pathogens against the host's first line of defense. PspA represents a major virulence factor and a promising vaccine candidate. Insights from the structure of the complex have implications for designing therapeutic strategies for treatment and prevention of pneumococcal diseases that remain a major public health problem worldwide.

show abstract

“…Similarly, goats and cows secrete human lysozyme [27] or human lactoferrin in their milk [13,28]. These two proteins have a broad antibacterial activity.…”

Section: Resistance To Diseasesmentioning

confidence: 99%

Preparation of recombinant proteins in milk to improve human and animal health

Soler¹,

Thépot²,

Rival‐Gervier³

et al. 2006

Reprod. Nutr. Dev.

View full text Add to dashboard Cite

-Milk is a very abundant source of proteins for animal and human consumption. Milk composition can be modified using transgenesis, including exogenous gene addition and endogenous gene inactivation. The study of milk protein genes has provided researchers with regulatory regions capable of efficiently and specifically driving the expression of foreign genes in milk. The projects underway are aimed at modifying milk composition, improving its nutritional value, reducing mammary infections, providing consumers with antipathogen proteins and preparing purified recombinant proteins for pharmaceutical use. The present paper summarises the current progress in this field. milk / recombinant proteins / animal and human health

show abstract

The protein structure of recombinant human lactoferrin produced in the milk of transgenic cows closely matches the structure of human milk-derived lactoferrin

Cited by 37 publications

References 34 publications

Transgenic Cows That Produce Recombinant Human Lactoferrin in Milk Are Not Protected from Experimental Escherichia coli Intramammary Infection

Transgenic Cows That Produce Recombinant Human Lactoferrin in Milk Are Not Protected from Experimental Escherichia coli Intramammary Infection

Structure of a Complex of Human Lactoferrin N-lobe with Pneumococcal Surface Protein A Provides Insight into Microbial Defense Mechanism

Preparation of recombinant proteins in milk to improve human and animal health

Contact Info

Product

Resources

About