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Birgitta Agerberth

Birgitta Agerberth

Birgitta Agerberth

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Research projects

Antimicrobial peptides/proteins

Antimicrobial peptides/proteins are widespread in nature and play a critical role in host defense. To investigate whether these components contribute to surface protection of newborns at birth, we have characterized antimicrobial polypeptides in vernix caseosa (vernix) and amniotic fluid (AF). Concentrated peptide/protein extracts were obtained from 11 samples of vernix and six samples of AF and analyzed for antimicrobial activity using an inhibition zone assay. Proteins/peptides in all vernix extracts exhibited strong antibacterial activity against Bacillus megaterium (strain Bm11), in addition to antifungal activity against Candida albicans, whereas AF-derived proteins/peptides showed only the former activity. Fractions obtained after separation by reverse-phase HPLC exhibited antibacterial activity, with the most pronounced activity in a fraction containing -defensins (HNP1-3). The presence of HNP1-3 was proved by dot blot analysis and confirmed by mass spectrometry. Lysozyme and ubiquitin were identified by sequence analysis in two fractions with antibacterial activity. Fractions of vernix and AF were also positive for LL-37 with dot blot and Western blot analyses, and one fraction apparently contained an extended form of LL-37. Interestingly, psoriasin, a calcium-binding protein that is up-regulated in psoriatic skin and was found recently to exhibit antimicrobial activity, was characterized in the vernix extract. The presence of all of these antimicrobial polypeptides in vernix suggests that they are important for surface defense and may have an active biologic role against microbial invasion at birth.

List of Publications

Chen, Z.-w., Agerberth, B., Gell, K., Andersson, M., Mutt, V., Östenson, C.-G., Efendic, S., Barros-Söderling, J., Persson, B. and Jörnvall, H.

Isolation and characterization of porcine diazepam-binding inhibitor, a polypeptide not only of cerebral occurrence but also common in intestinal tissues and with effects on regulation of insulin release.

Eur. J. Biochem. 174, 239-245, 1988.

Agerberth, B., Söderling-Barros, J., Jörnvall, H., Chen, Z.-w., Östenson, C.-G., Efendic, S. and Mutt, V.

Isolation and characterization of a 60-residue intestinal peptide structurally related to the pancreatic secretory type of trypsin inhibitor: Influence on insulin secretion.

Proc. Natl. Acad. Sci. USA, 86, 8590-8594, 1989.

Sillard, R., Agerberth, B., Mutt, V. and Jörnvall, H.

Sheep neuropeptide Y. A third structural type of a highly conserved peptide.

FEBS Lett., 258, 263-265, 1989.

Egestad, B. and Agerberth, B.

Fast atom bombardment mass spectrometry of the diazepam-binding inhibitor (DBI) polypeptide from porcine intestine.

J. Prot. Chem., 9, 330-331, 1990.

Aguirre, J.A., Fuxe, K., Agnati, L.F., Agerberth, B. and Mutt, V.

Vasopressor effects of intracerebroventricular injections of PEC-60, a novel porcine 60-residue intestinal peptide, in the awake unrestrained male rat.

Neurosci. Lett., 119, 129-131, 1990

Fuxe, K., Aguirre, J.A., Tinner, B., Agnati, L.F., Agerberth, B. and Mutt, V.

PEC-60, a novel porcine 60-residue intestinal peptide, reduces dopamine utilization in discrete parts of the neostriatum of the male rat following an intracerebroventricular injection.

Acta Physiol. Scand., 141, 139-140, 1991.

Agerberth, B., Östenson, C.-G., Efendic, S. and Jörnvall, H.

Pancreatic secretory trypsin inhibitor (PSTI) isolated from pig intestine: Influence on insulin and somatostatin release.

FEBS Lett., 281, 227-230, 1991.

Bergman, T., Agerberth, B. and Jörnvall, H.

Direct analysis of peptides and amino acids from capillary electrophoresis.

FEBS Lett., 283, 100-103, 1991.

Agerberth, B., Lee, J.-Y., Bergman, T., Carlquist, M., Boman, H.G., Mutt, V. and Jörnvall, H.

Amino acid sequence of PR-39. Isolation from pig intestine of a new member of the family of proline-arginine-rich antibacterial peptides.

Eur. J. Biochem., 202, 849-854, 1991.

Fuxe, K., Östenson, C.-G., Aguirre, J.A., Efendic, S., Agerberth, B. and Mutt. V.

Reserpine treatment increases PEC-60-like immunoreactivity in the substantia nigra of the male rat as determined by radioimmunoassay.

Acta Physiol. Scand., 143, 357-358, 1991.

von Euler, G., Ferre, S., von Euler M., Agerberth, B., Mutt, V. and Fuxe, K.

A trypsin inhibitor-like peptide PEC-60 reduces the affinity of dopamine D2 agonist binding sites in rat neostriatal membranes.

Eur. J. Pharmacol., 207, 365-366, 1991.

Nordlind, K., Bondesson, L., Agerberth, B. and Mutt, V.

Protecting effects of vasoactive intestinal polypeptide on lymphocytes against metal toxicity.

Immunopharm. Immunotoxic., 14, 323-330, 1992.

Metsis, M., Cintra, A., Solfrini, V., Ernfors, P., Bortolotti, F., Morrasutti, D.G., Östenson, C.-G., Efendic, S., Agerberth, B., Mutt, V., Persson, H. and Fuxe, K.

Molecular cloning of PEC-60 and expression of its mRNA and peptide in the gastrointestinal tract and immune system.

J. Biol. Chem., 267, 19829-19832, 1992

Boman, H.G., Agerberth, B. and Boman, A.

Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine.

Infect. Immun., 61, 2978-2984, 1993

Agerberth, B., Boman, A., Andersson, M., Jörnvall, H., Mutt, V. and Boman, H.G.

Isolation of three antibacterial peptides from pig intestine: gastric inhibitory polypeptide(7-42), diazepam-binding inhibitor(32-86) and a novel factor, peptide 3910.

Eur. J. Biochem. 216, 623-629, 1993.

Fuxe, K., Tinner, B., Metsis, M., Staines, W., Morassutti, D., Agnati, L.F., Östensson, C.-G., Efendic, S., Agerberth, B., Goldstein, M.

Generalized presence of a PEC-60-like peptide in catecholamine neurons.

Neuroreport. 5, 1817-1821, 1991.

Fuxe, K., Metsis, M., Ferré , S., O´Connor, W.T., Tinner, B., Cintra, A., Östenson, C.-G., Efendic, S., Agerberth, B., Tanganelli, S., Goldstein, M., Staines, W., Agnati, L.F. and Mutt, V.

PEC-60 and related peptides as hormones in the gastrointestinal tract and the immune system and as generalized cotransmitters in catecholamine neurons.

Biomed. Res., 17, 103-113, 1994.

Rimondini, R., O´Connor, W.T., Ferré , S., Sillard, R., Agerberth, B., Mutt, V., Ungerstedt, U. and Fuxe, K.

PEC-60 increases dopamine but not GABA release in the dorsolateral neostriatum of the halothane anaesthetized rat. An in vivo microdialysis study.

Neurosci. Lett., 177, 53-57, 1994.

Cabiaux, V., Agerberth, B., Johansson, J., Homblé , F., Goormaghtigh, E. and Ruysschaert, J-M.

Secondary structure and membrane interaction of PR-39: A proline-arginine-rich peptide.

Eur. J. Biochem., 224, 1019-1027, 1994.

Agerberth, B., Gunne, H., Odeberg, J., Kogner, P., Boman, H.G. and Gudmundsson, G.H.

FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis.

Proc. Natl. Acad. Sci. USA, 92, 195-199, 1995. 194 citations

Andersson*, M., Gunne*, H., Agerberth, B., Boman, A., Bergman, T., Sillard, R., Jörnvall, H., Mutt, V., Olsson, B., Wigzell, H., Dagerlind, Å ., Boman, H.G. and Gudmundsson, G.H. *Equal contribution

NK-lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity.

EMBO J., 14, 1615-1625, 1995.

Frohm, M., Gunne, H., Bergman, A.-C., Agerberth, B., Bergman, T., Boman, A., Lidén, S., Jörnvall, H. and Boman, H.G.

Biochemical and antibacterial analysis of human wound and blister fluid.

Eur. J. Biochem. 237, 86-92, 1996.

Andersson, M., Agerberth, B. and Gudmundsson, G.H.

Cytotoxic T lymphocytes: more weapons for new targets? Response.

Trends in Microbiology, 4, 94, 1996.

Gudmundsson, G.H., Agerberth, B., Odeberg, J., Olsson, B. and Salcedo, R.

The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes.

Eur. J. Biochem., 238, 325- 332, 1996.

Agerberth, B., Gunne, H., Odeberg, J., Kogner, P., Boman, H.G. and Gudmundsson, G.H.

PR-39, a proline-rich peptide antibiotic from pig, and FALL-39, a tentative human counterpart.

Vet. Immunol. Immunopathol., 54, 127-131, 1996.

Andersson, M., Gunne, H., Agerberth, B., Boman, A., Bergman, T., Olsson, B., Dagerlind, Å, Wigzell, H., Boman, H.G. and Gudmundsson, G.H.

NK-lysin, structure and function of a novel effector molecule of porcine T and NK cells.

Vet. Immunol. Immunopath., 54, 123-126, 1996.

Frohm*, M., Agerberth*, B., Ahangari, G., Ståhle-Bäckdahl, M. Lidén, S. Wigzell, H. and Gudmundsson, G.H. *Equal contribution

The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders.

J. Biol. Chem., 272, 15258-15263, 1997. 246 citations

Johansson, J., Gudmundsson, G.H., Rottenberg, M., Berndt, K.D. and Agerberth, B.

Conformation-dependent antibacterial activity of the naturally-occurring human peptide LL-37.

J. Biol. Chem., 273, 3718-3724, 1998. 120 citations

Wang, Y., Agerberth, B. and Johansson, J.

Structure and activity of the cathelicidin antibacterial proteins.

J. Protein Chem. 17, 522-523, 1998.

Wang Y, Agerberth, B., Löthgren, A., Almstedt, A. and Johansson, J.

Apolipoprotein A-I binds and inhibits the human antibacterial/cytotoxic peptide LL-37.

J. Biol. Chem., 273, 33115-33118, 1998

Agerberth, B., Grunewald, J., Castanos-Velez, E., Olsson, B., Jörnvall, H., Wigzell, H., Eklund, A. and Gudmundsson, G.H.

Antibacterial components in bronchoalveolar lavage fluid from healthy individuals and sarcoidosis patients.

Am. J. Respir. Crit. Care Med., 160, 283-290, 1999.

Oren, Z., Lerman, J.C., Gudmundsson, G.H., Agerberth, B. and Shai, Y.

Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity.

Biochem. J., 341, 501-513, 1999.

Lensmar, C., Nord, M., Gudmundsson, G.H., Roquet, A., Andersson, O., Jörnvall, H., Eklund, A., Grunewald, J. and Agerberth, B.

Decreased pulmonary levels of the anti-inflammatory Clara cell 16 kDa protein after induction of airway inflammation in asthmatics.

Cell. Mol. Life Sci., 57, 976-981. 2000.

Agerberth, B., Charo, J., Werr, J., Olsson, B., Idali, F., Lindbom, L., Kiessling, R., Jörnvall, H. Wigzell, H. and Gudmundsson, G.H.

The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins HNP 1-3 are expressed by specific lymphocyte and monocyte populations.

BLOOD, 96, 3086-3093, 2000. 162 citations

Dorschner, R.A., Pestonjamasp, V.K., Tamakuwala, S. Ohtake, T., Rudisill, J., Nizet, V., Agerberth, B., Gudmundsson, G.H. and Gallo, R.L.

Cutaneous injury induces the release of cathelicidin antimicrobial peptides active against Group A Streptococcus.

J. Invest. Dermatol. 117, 91-97, 2001.

Islam, D., Bandholtz, L., Nilsson, J., Wigzell, H., Christensson, B., Agerberth, B., and Gudmundsson, G.H.

Downregulation of bactericidal peptides in enteric infections: A novel immune escape mechanism with bacterial DNA as a potential regulator.

Nature Med. 7, 180-185, 2001. 116 citations

Wang, Y., Griffiths, W.J., Jörnvall, H., Agerberth, B. and Johansson, J.

Antibacterial peptides in stimulated human granulocytes: Characterisation of ubiquitinated histone H1A.

Eur. J. Biochem. 269, 512-518, 2002.

Marchini, G., Lindow, S., Brismar, H., Ståbi, B., Berggren, V., Ulfgren, A-K., Lonne-Rahm, S., Agerberth, B., Gudmundsson, G.H.

The human neonate is protected by an antimicrobial barrier: Peptide antibiotics are present in the skin and vernix caseosa.

Br. J. Dermatol. 147, 1127-1134, 2002.

Yoshio, H., Tollin, M., Gudmundsson, G.H., Lagercrantz, H., Jörnvall, H., Marchini, G. and Agerberth, B.

Antimicropbial polypeptides of human vernix caseosa and amniotic fluid: Implications for newborn innate defense.

Pediatr. Res. 53, 211-216, 2003.

Abraham-Nordling, M., Gudmundsson, G.H., Grunewald, J., Agerberth, B. and Griffiths, W.J.

Identification of a potent antibacterial factor isolated from bronchoalveolar lavage fluid: Guanidine, N-(3((aminoiminomethyl)amino)propyl)-N-dodecyl-, a potential source of error in the analysis of antibacterial agents.

Rapid Commun. Mass Spectrom., 17, 183-191, 2003.

Bandholtz, L., Guo, Y., Palmberg, C., Mattsson, K., Olsson, B., High, A., Shabanowitz, J., Hunt, D., Jörnvall, H., Wigzell, H., Agerberth*, B. and Gudmundsson*, G.H. *Equal contribution

Hsp90 binds CpG oligonucleotides directl: implications for hsp90 as a missing link in CpG signaling and recognition.

Cell. Mol. Life Sci., 60, 422-429, 2003.

Tollin, M., Bergman, P., Svenberg, T., Jörnvall, H., Gudmundsson, G.H. and Agerberth, B.

The first line defense of human colon mucosa includes several antimicrobial polypeptides.

Peptides, 24, 523-530, 2003.

Johansson, L., Rytkönen, A., Bergman, P., Albiger, B., Källström, H., Hökfelt, T., Agerberth, B., Cattaneo, R. and Jonsson, A.-B.

CD46 in meningococcal disease.

Science, 301, 373-375, 2003.

Schauber, J., Svanholm*, C., Termén*, S., Iffland, K., Menzel, T., Scheppach, W., Melcher, R., Agerberth, B., Luhrs, H. and Gudmundsson, G.H. *Equal contribution

The expression of the cathelicidin LL-37 is modulated by short-chain fatty acids in colonocytes and leukocytes: Relevance of signaling pathways.

GUT, 52, 735-741, 2003.

Termén, S., Tollin, M., Olsson, B., Svenberg, T., Agerberth, B. and Gudmundsson, G.H.

A model for innate antimicrobial peptides  Phylogeny, expression and activity of the rat cathelicidin.

Cell. Mol. Life Sci., 60, 536-549, 2003.

Wang, Y., Johansson, J., Agerberth, B., Jörnvall, H. and Griffiths, W.J.

The antimicrobial peptide LL-37 binds to the human plasma protein apolipoprotein A-I.

Rapid Commun. Mass Spectrom. 18, 588-589, 2004.

Wang Y., Herting, E., Agerberth, B. and Johansson, J.

Antibacterial activity of the cathelicidins prophenin (62-79) and LL-37 in the presence of a lung surfactant preparation.

Antimicrob. Agents Chemother. 48, 2097-100, 2004.

Starner, T.D., Agerberth, B., Gudmundsson , G.H. and McCray Jr, P.B.

Expression and activity of beta-defensins and LL37 in the developing human lung.

J. Immunol. 174, 1608-15, 2005.

Bergman, P., Termén, S., Johansson, L., Nyström, L., Arenas, E., Jonsson, A-B., Hökfelt, T., Gudmundsson, G.H. and Agerberth, B.

The antimicrobial peptide rCRAMP is present in the central nervous system of the rat.

J. Neurochem. 93, 1132-1140, 2005.

Bergman, P., Johansson, L., Asp, V., Plant, L., Gudmundsson, G.H., Jonsson, A-B. and Agerberth, B.

Neisseria gonorrhoeae downregulates the expression of the human antimicrobial peptide LL-37.

Cell. Microbiol. 7, 1009-1017, 2005.

Johansson, L., Rytkönen, A., Wan, H., Bergman, P., Plant, L., Agerberth, B., Hökfelt, T. and Jonsson, A-B.

Human-like immune responses in CD46 transgenic mice.

J. Immunol. 175, 433-440, 2005.

Bergsson, G., Agerberth, B., Jörnvall, H. and Gudmundsson, G.H.

Isolation and identification of antimicrobial components from the epidermal mucus of the Atlantic cod (Gadu morhua).

FEBS J. 272, 4960-9, 2005.

Tollin, M., Bergsson, G., Kai-Larsen, Y., Lengqvist, J., Sjövall, J., Griffiths, W., Skúladóttir, G.V., Haraldsson, Á., Jörnvall, H., Gudmundsson, G.H. and Agerberth, B.

Vernix caseosa as a multi-component defence system based on polypeptides, lipids and their interactions.

Cell. Mol. Life Sci. 62, 2390-2399, 2005.

Agerberth, B., Buentke, E., Bergman, P., Eshaghi, H., Gabrielsson, S., Gudmundsson, G.H. and Scheynius, A.

Malassezia sympodialis differently affects the expression of LL-37 in dendritic cells from atopic eczema patients and healthy individuals.

Allergy 61, 422-430, 2006.

Bandholtz, L., Jacobsson Ekman G., Vilhelmsson, M., Buentke, E., Agerberth, B., Scheynius, A. and Gudmundsson, G.H.

Antimicrobial peptide LL-37 internalized by immature human dendritic cells alters their phenotype.

Scand. J. Immunol. 63, 410-419, 2006.

Edfeldt, E., Agerberth B., Rottenberg, M.E., Gudmundsson, G.H., Wang, X-B., Mandal, K., Xu, Q and Yan, Z-q.

Involvement of the antimicrobial peptide LL-37 in human atherosclerosis.

Arterioscler Thromb Vasc Biol. 26, 1551-7, 2006.

Cromek, M., Slamová, Z., Bergman, P., Kovács, L., Podracká, L., Ehrén, I., Hökfelt, T., Gudmundsson, G.H., Gallo, R.L., Agerberth, B. and Brauner, A.

Cathelicidin antimicrobial peptide protects the urinary tract against invasive bacterial infection.

Nature Med. 12, 636-641, 2006.

Raqib, R., Sarker, P., Bergman, P., Ara, G., Lindh, M., Sack, D.A., Islam, K.M.N., Gudmundsson, G.H., Andersson, J and Agerberth, B.

Improved outcome in shigellosis via butyrate-mediated induction of an endogenous peptide antibiotic.

Proc. Natl. Acad. Sci. USA. 103, 9178-9183, 2006.

Tollin, M., Jägerbrink, T., Haraldsson, A., Agerberth, B. and Jörnvall, H.

Proteome analysis of vernix caseosa.

Pediatr. Res. 60, 430-4, 2006.

Bergman, P., Johansson, L., Wan, H., Jones, A., Gallo, R.L., Gudmundsson, G.H., Hökfelt, T., Jonsson, A-B and Agerberth, B.

Induction of the antimicrobial peptide CRAMP in the blood brain barrier and meninges after meningococcal infection.

Infect. Immun. 74, 6982-91, 2006.

Wan, M., Sabrish, A., Wetterholm, A., Agerberth, B. and Haeggström, J.

Leukotriene B4 triggers release of the cathelicidin LL-37 from human neutrophils: novel lipid-peptide interactions in innate immune responses.

FASEB J. 21, 2897-2905, 2007.

Kai-Larsen, K., Bergsson, G., Gudmundsson, G.H., Printz, G., Jörnvall, H., Marchini, G. and Agerberth, B.

Antimicrobial components of neonatal gut affected upon colonization.

Pediatr. Res. 61, 530-536, 2007.

Bergman, P., Walter-Jallow, L., Broliden, K., Agerberth, B. and Söderlund, J.

The antimicrobial peptide LL-37 inhibits HIV-1 replication.

Current HIV Research 5, 413-418, 2007.

Termén, S., Tollin, M., Rodriguez, E., Sveinsdottir, S.H., Jóhannesson, B., Cederlund, A., Sjövall, J., Agerberth, B. and Gudmundsson, G.H.

PU.1 and bacterial metabolites regulate the human CAMP encoding antimicrobial peptide LL-37 in colon epithelial cells.

Mol. Immunol. 45, 3947-55, 2008.

Soehnlein, O., Kai-Larsen, Y., Frithiof, R., Sorensen, O.E., Kenne, E., Scharffetter-Kochanek, K., Eriksson, E.E., Herwald, H., Agerberth, B. and Lindbom, L.

Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages.

J. Clin. Invest. 118, 3491-3502, 2008.

Ballardini, N., Johansson, C., Lilja, G., Lindh, M., Scheynius, A. Linde, Y., and Agerberth, B.

Enhanced expression of the antimicrobial peptide LL-37 in leisonal skin of adults with atopic eczema.

Br. J. Dermatol. Accepted

Reviews and book chapters

Agerberth, Birgitta. Institutet, Stockholm 1993.

Isolation and characterization of biologically active polypeptides. Emphasis on hormon-like and antibacterial activities.

Thesis, Karolinska Institutet, Stockholm 1993.

Gudmundsson, G.H. and Agerberth, B.

Neutrophil antibacterial peptides, multifunctional effector molecules in the mammmalian immune system.

Review J. Immun. Meth., 232, 45-54, 1999.

Agerberth, B. and Gudmundsson, G.H.

Human cathelicidin antimicrobial peptide LL-37.

ed Oppenheim, J.J. and Feldman, M. Academic press. 2003.

Gudmundsson, G.H. and Agerberth, B.

Biology and expression of the human cathelicidin LL-37

in Mammalian Antimicrobial Peptides ed Devine, D.A. and Hancock, R.E.W. Cambridge University Press. 2004.

Yoshio H., Lagercrantz H., Gudmundsson G.H and Agerberth B.

First line of defense in early human life.

Semin Perinatol. 28, 304-11, 2004.

Gudmundsson, G.H. and Agerberth, B.

Antimirobial peptides in human blood

in Antimicrobial Peptides in Human Health and Disease ed Gallo, R.L. Horizon Scientific Press/Caister Academic 2005.

Agerberth, B. and Gudmundsson. G.H.

Host antimicrobial defence peptides in human disease.

Curr Top Microbiol Immunol. 306, 67-90, 2006.

Kai-Larsen Y. and Agerberth, B.

The role of the multifunctional peptide LL-37 in host defence.

Frontiers in Bioscience, 13, 3760-3767, 2008.

Bergman, P., Gudmundsson, G.H. and Agerberth, B.

Naturlig immunitet-första linjens försvar. Ny behandling mot infektioner och autoimmuna sjukdomar i sikte.

Läkartidningen, nr. 34, 2008, volym 105.

Last modified by: Sarah Löwhagen 2011-03-03
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