Lactoferrin (Lf) is a single-chain iron-binding glycopro-
tein, which is present in the secondary granules of neu-
trophils and external secretions like milk, tears, saliva,
pancreatic juice, vaginal secretion and seminal fluid. It is
a principal component of the first line host defence
against infection and inflammation [1]. Lf has many bio-
logical functions, such as modulation of iron absorption,
anti-microbial activity, immunoregulation, and growth
promotion [2, 3]. In human milk, Lf concentrations are
high in colostrum, where its main physiological role is to
inhibit the growth of pathogenic bacteria in the mamma-
ry gland of the mother and the intestinal tract of the suck-
ling infant, and to mediate transport of iron from the moth-
er to the newborn [4].
In lactating cows, the bovine Lf (bLf) level in milk
varies from 0.02 to 0.35 mg/mL [5–7]. Much higher con-
centrations of bLf are found in colostrum and dry-period
secretion [8], where Lf is one of the most important factors
in the defence of the mammary gland [9]. The concentra-
tion of Lf found in the first milking after calving was
0.83 mg/mL, decreasing sharply during the first days of
lactation [8]. The health status of the udder also affects Lf
levels in milk so that during intra-mammary infections Lf
is markedly increased [10, 11].
The first recombinant human Lf (rhLf) bull was pro-
duced by the Pharming Group NV (The Netherlands) in
1990 [12]. It was produced by microinjection, and the hLf
gene was under the control of the bovine aS1-casein pro-
moter so that expression of rhLf occurred in the mamma-
ry gland [13]. According to van Berkel et al. [14], in hor-
mone-induced lactation of the various animal lines, rhLf
concentrations of milk were between 0.3 and 2.8 mg/mL
and remained constant throughout the lactation period.
Recombinant and natural hLf are structurally and func-
tionally similar, and the homology at the protein level of
hLf and bLf is 69% [4]. rhLf of the transgenic cows and nat-
ural hLf show similar structural and functional properties
in vitro [15].
The study reported here is a part of an investigation on
the protective effects of rhLf against mastitis. The specif-
ic aim here was to study the rhLf and bLf concentrations
in milk of rhLf-transgenic cows during normal lactation.
Seven Holstein-Friesian transgenic cows inseminated
Short Communication
Human and bovine lactoferrins in the milk of recombinant
human lactoferrin-transgenic dairy cows during lactation
Paula Hyvönen
1
, Leena Suojala
2
, Johanna Haaranen
1
, Atte von Wright
1
and Satu Pyörälä
2
1
Institute of Applied Biotechnology, University of Kuopio, Kuopio, Finland
2
Department of Clinical Veterinary Sciences, Saari Unit, Faculty of Veterinary Medicine, University of Helsinki, Finland
Seven Friesian human lactoferrin (hLf)-transgenic primiparous dairy cows expressing recombi-
nant hLf (rhLf) in their milk were included in the study. After calving, concentrations of rhLf and
bovine LF (bLf) in the milk, somatic cell count and milk yield were determined. The concentration
of rhLf was found to be constant, about 2.9 mg/mL, throughout the early lactation period of 3
months. The concentration of bLf in colostrum was higher after calving, but decreased rapidly dur-
ing the first days of lactation. The mean concentration of bLf was 0.15 mg/mL, but concentrations
varied between cows from 0.07 mg/mL to 0.26 mg/mL. Based on that, it may be possible to im-
prove the non-specific host defence mechanism in the mammary gland of dairy cows by enhanc-
ing the content of rhLf in the milk.
Keywords: Transgenic cows · Lactoferrin · Lactation
Correspondence: Paula Hyvönen, DVM, University of Kuopio, Insitute of
Applied Biotechnology, P.O.Box 1627, FIN-70211 Kuopio, Finland
E-mail: paula.hyvonen@uku.fi
Fax: +358-17-163322
Abbreviations: bLf, bovine lactoferrin; rhLf, recombinant human lactoferrin;
SCC, somatic cell count
Received 14 February 2006
Revised 5 March 2006
Accepted 6 March 2006
Biotechnology
Journal
DOI 10.1002/biot.200600016 Biotechnol. J. 2006, 1, 410–412
410 © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim