Table Of ContentLactoferrin
Experimental Biology and Medicine
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Lactoferrin
Interactions and Biological Functions
Edited by
T. William Hutchens
Department ofF ood Science and Technology,
University of California, Davis, CA
and
Bo Lonnerdal
Department of Nutrition,
University of California, Davis, CA
*-
Humana Press • Totowa, New Jersey
© 1997 Humana Press Inc.
Sotlcover reprint ofthe hardcover 1s t edition 1997
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Cover illustration: Figure 4 in "Difference in Binding and Fate of Lactotransferrin in Jurkat
Human Lymphoblastic T-Cells and in T-47D Human Breast Cancer Cells," by Bao Yuan Bi,
Elisabeth Elass, Dominique Legrand, Florence Deplace, Genevieve Spik, and Joel Mazurier.
Cover design by Patricia F. Cleary.
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Library of Congress Cataloging in Publication Data
Lactoferrin: interactions and biological function/edited by T. William Hutchens and Bo
Lonnerdal.
p. cm.-(Contemporary neuroscience)
Based on the Second International Symposium on Lactoferrin Structure and Function,
held in Honolulu, Hawaii, 1995.
Includes index.
ISBN-13: 978-1-4612-8439-0 e-1SBN-13: 978-1-4612-3956-7
DOl: 10.1007/978-1-4612-3956-7
1. Lactoferrins-Congresses. I. Hutchens, T. William. II. Lonnerdal, Bo, 1938-
III. International Symposium on Lactoferrin Structure and Function (2nd: 1995:
Honolulu, Hawaii). IV. Series.
[DNLM: 1. Lactoferrin-physiology-congresses. QU 55 L1505 1997]
QP552.L345L326 1997
572'.6-dc21
DNLM/DLC
for Library of Congress 96-52990
CIP
Preface
The number of investigators focusing their attention on
lactoferrin has increased dramatically in recent years. Lactoferrin
is a protein with more than one known structure and a number of
proposed biological functions, including several with important
regulatory consequences. In many ways it has been an easy pro
tein to investigate; however, there have been difficulties under
standing specific structure / function relationships, particularly as
it functions in vivo. Research funding dedicated to this protein
has previously been limited, but is now increasing. As lactoferrin
begins to emerge formally as a protein of significance to the medi
cal profession and industry, it is more important than ever to coor
dinate and integrate research efforts whenever possible and to
share the results of these efforts within the expanding array of
medical and scientific diSciplines involved. It was our intention to
provide a forum to summarize and disseminate the most recent
advances in this field.
Included in Lactoferrin: Interactions and Biological Functions are
selected presentations representing the many disciplines involved
in defining lactoferrin function in terms of its known structural
features, including its carbohydrate side-chains, receptor binding
sites, its capacity to bind different metal ions, and other newly
discovered bioactive domains. Several of the possible physiologi
cal functions of lactoferrin are described and summarized in
detail, including the role of laetoferrin in bacterial killing, its in
volvement in cell growth and proliferation, in the modulation of
immune function, and in iron absorption. The biological functions
of lactoferrin in several different cell types and tissues are empha
sized. New techniques for the investigation of lactoferrin process
ing and distribution in vivo are also introduced. New knowledge
regarding the molecular biology of lactoferrin, including regula-
v
vi Preface
tion of gene expression, are addressed, as are commercially viable
large-scale production techniques and important new industrial
applications.
Lactaferrin: Interactions and Biological Functions should provide
the interested reader a thorough insight into our present know
ledge of lactoferrin. Particular attention was given to lactoferrin
functions in the regulation of normal and diseased states.
Acknowledgments
The organizers and participants would like to thank the
following sponsors of the Second International Symposium on
Lactoferrin: Interactions and Biological Functions: Agennix, Inc.,
DMV International, Milupa AG, Morinaga Milk Industry Co.,
Wei-Chuan Foods, and Wyeth-Ayerst Research.
T. William Hutchens
Bo Lonnerdal
Contents
Preface .......................................................................................................... v
List of Contributors .................................................................................. xi
PART I: LACTOFERRIN STRUCTURE AND FUNCTION ............•.....•••....... 1
1. Lactoferrin Structure-Function Relationships:
An Overview
Jeremy H. Brock ................................................................................... 3
2. Altered Domain Closure and Iron Binding
in Lactoferrin Mutants
H. Rick Faber, Bryan F. Anderson, Heather M. Baker,
Tony Bland, Catherine L. Day, Hale Nicholson,
Steven Shewry, John W. Tweedie, and Edward N. Baker ....... 25
3. Affinity Mass Spectrometry: Probes with Surfaces
Enhanced for Affinity Capture (SEA C) of Lactoferrin
Tai-Tung Yip and T. William Hutchens ......................................... 39
PART II: LACTOFERRIN G ENE EXPRESSION ........................................ 59
4. Variants and Biotechnological Use
of the Bovine Lactoferrin-Encoding Gene
Hans-Martin Seyfert, Uta Klu{3mann, Uta Maria Steinhoff,
lens Vanselow, Dirk Koczan, and Gerd Hobom ...................... 61
5. Posttranscriptional Regulation of Bovine
and Human Lactoferrin: Species Differences
and Influence of mRNA Regions
Floyd L. Schanbacher, Surapon Pattanajitvilai,
and Margaret C. Neville .............................................................. 81
6. Mutagenesis of Human Lactoferrin
and Expression in Baby Hamster Kidney Cells
John W. Tweedie, Edward N. Baker, Catherine L. Day,
Bhavwanti Sheth, and H. Hale Nicholson ............................... 97
vzz
viii Contents
7. Structural Determination of Two N-Linked Glycans
Isolated from Recombinant Human Lactoferrin
Expressed in BHK Cells
Dominique Legrand, Valerie Salmon, Bernadette Coddeville,
Monique Benai'ssa, Yves Plancke, and Genevieve Spik ........ 111
8. Distribution of the Iron-Binding Protein
Lactoferrin in the Pathological
L~sions
of Neurodegenerative Diseases
Beatrice Leveugle, Genevieve Spik, Daniel P. Perl,
Constantin Bouras, Howard M. Fillit,
and Patrick R. Hot ..................................................................... 119
9. Lactoferrin Almost Absent from Lactating
Rat Mammary Gland Is Replaced by Transferrin
Annick Pierce, Hector Escriva, Bernadette Coddeville,
Monique Benai'ssa, Didier Leger, Genevieve Spik,
and Mercedes Pamblanco .......................................................... 125
10. Estrogen Regulation of Human Lactoferrin Gene
Activity: Transcriptional Synergism Between
Estrogen Receptorand Related Orphan Receptor
Christina T. Teng and Nengyu Yang ............................................. 135
11. Expression and Functional Analysis
of Recombinant Human Lactoferrin
Pauline P. Ward, Christopher S. Piddington,
Grainne Cunningham, Xiaodong Zhou,
Roger D. Wyatt, and Orla M. Conneely ................................. 155
12. Structural and Functional Flexibility
of Lactoferrin
Edward N. Baker, Bryan F. Anderson, Heather M. Baker,
Rick Faber, Clyde A. Smith,
and Andrew J. Sutherland-Smith ............................................. 177
13. Difference in Binding and Fate of Lactotransferrin
in Jurkat Human Lymphoblastic T-Cells
and in T-47D Human Breast Cancer Cells
Bao Yuan Bi, Elisabeth Elass, Dominique Legrand,
Florence Deplace, Genevieve Spik, and Joel Mazurier ......... 193
Contents zx
14. The Impact of Phagocyte-Lactoferrin Interactions
on Inflammation
Bradley E. Britigan, Troy S. Lewis, Oyebode Olakanmi,
Michael L. McCormick, and Rachel A. Miller ...................... 211
15. Regulation of Lymphocyte Proliferation
by Lactoferrin
Jeremy H. Brock and Abdelhakim Djeha .................................... 233
16. Recombinant Human Lactoferrin and Its Variants:
Receptor Binding in Human Intestinal Brush-Border
Membranes
Suhasini lyer, Bo Lonnerdal, Catharine Day,
Edward N. Baker, John Tweedie, Tai-Tung Yip,
and T. William Hutchens .......................................................... 245
PART III: FUNCTIONS RELATED TO LACTOFERRIN INTERACTIONS
WITH PROKARYOTIC AND EUKARYOTIC CELLS .......................... 257
17. Influence of Lactoferrin
on Host-Microbe Interactions
Satyanarayan Naidu and Roland R. Arnold ............................. 259
18. Bacterial Lactoferrin Receptors in the Neisseriaceae
Robert A. Bonnah, Rong-hua Yu,
and Anthony B. Schryvers ......................................................... 277
19. Bacteriostatic Effects of Orally Administered
Bovine Lactoferrin on Intestinal Bacteria
in the Gut of Mice Fed Bovine Milk
Susumu Teraguchi, Kouichirou Shin, Kazuhiro Ozawa,
Satoko Nakamura, Yasuo Fukuwatari,
Seiichi Shimamura, and Mamoru Tomita .............................. 303
20. Functional Significance of the Binding
of Lactoferrin to DNA
Philip Furmanski, Jianglin He, Li Ying, Joann Bezault,
Ramesh Bhimani, and Kin/an Ho ............................................ 313
21. Specific Binding of Ferrilactoferrin
and Ferritransferrin in the Protozoan Leishmania
chagasi
Michael L. McCormick, Mary E. Wilson, Troy S. Lewis,
Robert W. Vorhies, and Bradley E. Britigan .......................... 333
x Contents
PART IV: LACTOFERRIN METABOLISM ................................................. 343
22. Observations on the Metabolism
and Cellular Interactions of Lactoferrin
Erwin Regoeczi ................................................................................ 345
23. Lactoferrin as a Possible Transcriptional Regulator:
Downmodulation of the Granulocyte-Macrophage
Colony-Stimulating Factor Promoter
Silvana Penco, Sandra Pastorino, Claudia Gramigni,
Giovanna Bianchi-Scarra, Roberto Ravazzolo,
and Cecilia Garre ........................................................................ 359
PART V: THE USE OF LACTOFERRIN AS A FOOD ADDITIVE ............ 375
24. Modification of Infant Formula: The Case
of Lactoferrin
Eric L. Lien ....................................................................................... 377
25. Lactoferrin in Infant Formulas: How and Why?
Gunther Sawatzki ........................................................................... 389
Index ......................................................................................................... 399
