Skip to main content
Erschienen in: Archives of Dermatological Research 5/2006

01.10.2006 | Original Paper

Hyaluronic acid inhibits the adherence and growth of monolayer keratinocytes but does not affect the growth of keratinocyte epithelium

verfasst von: Ilkka T. Harvima, Hanna Heikura, Mika Hyttinen, Anita Naukkarinen

Erschienen in: Archives of Dermatological Research | Ausgabe 5/2006

Einloggen, um Zugang zu erhalten

Abstract

Hyaluronic acid (HA) is involved in epidermal biology but evidence for its functional significance is sparse. In this study, low-calcium monolayer and high-calcium epithelium cultures of human keratinocytes were used to study the effect of up to four different HA preparations on keratinocyte growth and on the adherence of proliferating keratinocytes onto the plastic surface coated with different matrix proteins. In suboptimally growing monolayer culture, up to 1,000 μg/ml rooster comb HA and streptococcus equi HA inhibited keratinocyte growth. Instead, all HA preparations tested did not affect the growth and migration of keratinocyte epithelium using optimal or suboptimal growth conditions. In the cell adherence assays, up to 1,000 μg/ml rooster comb HA and streptococcus equi HA inhibited the keratinocyte adherence onto the fibronectin- and collagen-coated substratum. In contrast to other HA preparations, HA from human umbilical cord did not affect the growth of monolayer keratinocytes and it increased markedly the cell adherence onto the collagen-coated substratum. This increase, however, can be attributed to chonroitin sulphate proteoglycan contaminant present in this HA preparation. In conclusion, HA can inhibit the growth and adherence of proliferating monolayer keratinocytes, but it has no apparent effect on the growth and migration of keratinocyte epithelium.
Literatur
1.
Zurück zum Zitat Ackermann L, Harvima IT (1998) Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-α and their degranulation is associated with expression of ICAM-1 in the epidermis. Arch Dermatol Res 290:353–359PubMedCrossRef Ackermann L, Harvima IT (1998) Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-α and their degranulation is associated with expression of ICAM-1 in the epidermis. Arch Dermatol Res 290:353–359PubMedCrossRef
2.
Zurück zum Zitat Akiyama H, Saito M, Qiu G, Toida T, Imanari T (1994) Analytical studies on hyaluronic acid synthesis by normal human epidermal keratinocytes cultured in a serum-free medium. Biol Pharm Bull 17:361–364PubMed Akiyama H, Saito M, Qiu G, Toida T, Imanari T (1994) Analytical studies on hyaluronic acid synthesis by normal human epidermal keratinocytes cultured in a serum-free medium. Biol Pharm Bull 17:361–364PubMed
3.
Zurück zum Zitat Berman B, Ostrovsky O, Shlissel M, Lang T, Regan D, Vlodavsky I, Ishai-Michaeli R, Ron D (1999) Similarities and differences between the effects of heparin and glypican-1 on the bioactivity of acidic fibroblast growth factor and the keratinocyte growth factor. J Biol Chem 274:36132–36138PubMedCrossRef Berman B, Ostrovsky O, Shlissel M, Lang T, Regan D, Vlodavsky I, Ishai-Michaeli R, Ron D (1999) Similarities and differences between the effects of heparin and glypican-1 on the bioactivity of acidic fibroblast growth factor and the keratinocyte growth factor. J Biol Chem 274:36132–36138PubMedCrossRef
4.
Zurück zum Zitat Bettinger DA, Mast B (1996) Hyaluronic acid impedes reepithelialization of skin graft donor sites. J Burn Care Rehabil 17:302–304PubMedCrossRef Bettinger DA, Mast B (1996) Hyaluronic acid impedes reepithelialization of skin graft donor sites. J Burn Care Rehabil 17:302–304PubMedCrossRef
5.
Zurück zum Zitat Bonaldo P, Russo V, Bucciotti F, Doliana R, Colombatti A (1990) Structural and functional features of the alpha 3 chain indicate a bridging role for chicken collagen VI in connective tissue. Biochemistry 29:1245–1254PubMedCrossRef Bonaldo P, Russo V, Bucciotti F, Doliana R, Colombatti A (1990) Structural and functional features of the alpha 3 chain indicate a bridging role for chicken collagen VI in connective tissue. Biochemistry 29:1245–1254PubMedCrossRef
6.
Zurück zum Zitat Brown MB, Jones SA (2005) Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin. JEADV 19:308–318PubMed Brown MB, Jones SA (2005) Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin. JEADV 19:308–318PubMed
7.
Zurück zum Zitat Brown TJ, Alcorn D, Fraser JRE (1999) Absorption of hyaluronan applied to the surface of intact skin. J Invest Dermatol 113:740–746PubMedCrossRef Brown TJ, Alcorn D, Fraser JRE (1999) Absorption of hyaluronan applied to the surface of intact skin. J Invest Dermatol 113:740–746PubMedCrossRef
8.
Zurück zum Zitat Edmonds M, Bates M, Doxford M, Gough A, Foster A (2000) New treatments in ulcer healing and wound infection. Diabetes Metab Res Rev 16(Suppl 1):S51–S54PubMedCrossRef Edmonds M, Bates M, Doxford M, Gough A, Foster A (2000) New treatments in ulcer healing and wound infection. Diabetes Metab Res Rev 16(Suppl 1):S51–S54PubMedCrossRef
9.
Zurück zum Zitat Frost SJ, Weigel PH (1990) Binding of hyaluronic acid to mammalian fibrinogens. Biochim Biophys Acta 1034:39–45PubMed Frost SJ, Weigel PH (1990) Binding of hyaluronic acid to mammalian fibrinogens. Biochim Biophys Acta 1034:39–45PubMed
10.
Zurück zum Zitat Harvima IT, Virnes S, Kauppinen L, Huttunen M, Kivinen P, Niskanen L, Horsmanheimo M (1999) Cultured allogeneic skin cells are effective in the treatment of chronic diabetic leg and foot ulcers. Acta Derm Venereol (Stockh) 79:217–220CrossRef Harvima IT, Virnes S, Kauppinen L, Huttunen M, Kivinen P, Niskanen L, Horsmanheimo M (1999) Cultured allogeneic skin cells are effective in the treatment of chronic diabetic leg and foot ulcers. Acta Derm Venereol (Stockh) 79:217–220CrossRef
11.
Zurück zum Zitat Harvima IT, Lappalainen K, Hirvonen M-R, Mättö M, Kivinen PK, Hyttinen M, Pelkonen J, Naukkarinen A (2004) Heparin modulates the growth and adherence and augments the growth-inhibitory action of TNF-α on cultured human keratinocytes. J Cell Biochem 92:372–386PubMedCrossRef Harvima IT, Lappalainen K, Hirvonen M-R, Mättö M, Kivinen PK, Hyttinen M, Pelkonen J, Naukkarinen A (2004) Heparin modulates the growth and adherence and augments the growth-inhibitory action of TNF-α on cultured human keratinocytes. J Cell Biochem 92:372–386PubMedCrossRef
12.
Zurück zum Zitat Huttunen M, Hyttinen M, Nilsson G, Butterfield JH, Horsmanheimo M, Harvima IT (2001) Inhibition of keratinocyte growth in cell culture and whole skin culture by mast cell mediators. Exp Dermatol 10:184–192PubMedCrossRef Huttunen M, Hyttinen M, Nilsson G, Butterfield JH, Horsmanheimo M, Harvima IT (2001) Inhibition of keratinocyte growth in cell culture and whole skin culture by mast cell mediators. Exp Dermatol 10:184–192PubMedCrossRef
13.
Zurück zum Zitat Huttunen M, Harvima IT (2005) Mast cell tryptase and chymase in chronic leg ulcers: chymase is potentially destructive to epithelium and is controlled by proteinase inhibitors. Br J Dermatol 152:1149–1160PubMedCrossRef Huttunen M, Harvima IT (2005) Mast cell tryptase and chymase in chronic leg ulcers: chymase is potentially destructive to epithelium and is controlled by proteinase inhibitors. Br J Dermatol 152:1149–1160PubMedCrossRef
14.
Zurück zum Zitat Isemura M, Yosizawa Z, Koide T, Ono T (1982) Interaction of fibronectin and its proteolytic fragments with hyaluronic acid. J Biochem 91:731–734PubMed Isemura M, Yosizawa Z, Koide T, Ono T (1982) Interaction of fibronectin and its proteolytic fragments with hyaluronic acid. J Biochem 91:731–734PubMed
15.
Zurück zum Zitat Isnard N, Legeais J-M, Renard G, Robert L (2001) Effect of hyaluronan on MMP expression and activation. Cell Biol Int 25:735–739PubMedCrossRef Isnard N, Legeais J-M, Renard G, Robert L (2001) Effect of hyaluronan on MMP expression and activation. Cell Biol Int 25:735–739PubMedCrossRef
16.
Zurück zum Zitat John Chen WY, Abatangelo G (1999) Functions of hyaluronan in wound repair. Wound Repair Regen 7:79–89CrossRef John Chen WY, Abatangelo G (1999) Functions of hyaluronan in wound repair. Wound Repair Regen 7:79–89CrossRef
18.
Zurück zum Zitat Keene DR, Ridgway CC, Iozzo RV (1998) Type VI microfilaments interact with a specific region of banded collagen fibrils in skin. J Histochem Cytochem 46:215–220PubMed Keene DR, Ridgway CC, Iozzo RV (1998) Type VI microfilaments interact with a specific region of banded collagen fibrils in skin. J Histochem Cytochem 46:215–220PubMed
19.
Zurück zum Zitat Lundin Å, Berne B, Michaëlsson G (1992) Topical retinoic acid treatment of photoaged skin: its effects on hyaluronan distribution in epidermis and on hyaluronan and retinoic acid in suction blister fluid. Acta Derm Venereol (Stockh) 72:423–427 Lundin Å, Berne B, Michaëlsson G (1992) Topical retinoic acid treatment of photoaged skin: its effects on hyaluronan distribution in epidermis and on hyaluronan and retinoic acid in suction blister fluid. Acta Derm Venereol (Stockh) 72:423–427
20.
Zurück zum Zitat Manuskiatti W, Maibach HI (1996) Hyaluronic acid and skin: wound healing and aging. Int J Dermatol 35:539–544PubMedCrossRef Manuskiatti W, Maibach HI (1996) Hyaluronic acid and skin: wound healing and aging. Int J Dermatol 35:539–544PubMedCrossRef
21.
Zurück zum Zitat McDevitt CA, Marcelino J, Tucker L (1991) Interaction of intact type VI collagen with hyaluronan. FEBS Lett 294:167–170PubMedCrossRef McDevitt CA, Marcelino J, Tucker L (1991) Interaction of intact type VI collagen with hyaluronan. FEBS Lett 294:167–170PubMedCrossRef
22.
Zurück zum Zitat Meyer LJ, Russell SB, Russell JD, Trupin JS, Egbert BM, Shuster S, Stern R (2000) Reduced hyaluronan in keloid tissue and cultured keloid fibroblasts. J Invest Dermatol 114:953–959PubMedCrossRef Meyer LJ, Russell SB, Russell JD, Trupin JS, Egbert BM, Shuster S, Stern R (2000) Reduced hyaluronan in keloid tissue and cultured keloid fibroblasts. J Invest Dermatol 114:953–959PubMedCrossRef
23.
Zurück zum Zitat Nakamura M, Mishima H, Nishida T, Otori T (1994) Binding of hyaluronan to plasma fibronectin increases the attachment of corneal epithelial cells to a fibronectin matrix. J Cell Physiol 159:415–422PubMedCrossRef Nakamura M, Mishima H, Nishida T, Otori T (1994) Binding of hyaluronan to plasma fibronectin increases the attachment of corneal epithelial cells to a fibronectin matrix. J Cell Physiol 159:415–422PubMedCrossRef
24.
Zurück zum Zitat Oksala O, Salo T, Tammi R, Häkkinen L, Jalkanen M, Inki P, Larjava H (1995) Expression of proteoglycans and hyaluronan during wound healing. J Histochem Cytochem 43:125–135PubMed Oksala O, Salo T, Tammi R, Häkkinen L, Jalkanen M, Inki P, Larjava H (1995) Expression of proteoglycans and hyaluronan during wound healing. J Histochem Cytochem 43:125–135PubMed
25.
Zurück zum Zitat Otto W (1994) Determination of cell number by DNA content. In: Leigh IM, Watt FM (eds) Keratinocyte Handbook. Cambridge University Press, Cambridge, pp 89–90 Otto W (1994) Determination of cell number by DNA content. In: Leigh IM, Watt FM (eds) Keratinocyte Handbook. Cambridge University Press, Cambridge, pp 89–90
26.
Zurück zum Zitat Piepkorn M, Fleckman P, Carney H, Linker A (1988) Glycosaminoglycan synthesis by human keratinocytes: cell growth and medium calcium effects. J Invest Dermatol 91:492–498PubMedCrossRef Piepkorn M, Fleckman P, Carney H, Linker A (1988) Glycosaminoglycan synthesis by human keratinocytes: cell growth and medium calcium effects. J Invest Dermatol 91:492–498PubMedCrossRef
27.
Zurück zum Zitat Piepkorn M, Lo C, Plowman G (1994) Amphiregulin-dependent proliferation of cultured human keratinocytes: autocrine growth, the effects of exogenous recombinant cytokine, and apparent requirement for heparin-like glycosaminoglycans. J Cell Physiol 159:114–120PubMedCrossRef Piepkorn M, Lo C, Plowman G (1994) Amphiregulin-dependent proliferation of cultured human keratinocytes: autocrine growth, the effects of exogenous recombinant cytokine, and apparent requirement for heparin-like glycosaminoglycans. J Cell Physiol 159:114–120PubMedCrossRef
28.
Zurück zum Zitat Pillai S, Bikle DD, Eessalu TE, Aggarwal BB, Elias PM (1989) Binding and biological effects of tumor necrosis factor alpha on cultured human neonatal foreskin keratinocytes. J Clin Invest 83:816–821PubMedCrossRef Pillai S, Bikle DD, Eessalu TE, Aggarwal BB, Elias PM (1989) Binding and biological effects of tumor necrosis factor alpha on cultured human neonatal foreskin keratinocytes. J Clin Invest 83:816–821PubMedCrossRef
29.
Zurück zum Zitat Pillai S, Gilliam L, Conrad HE, Holleran WM (1994) Heparin and its non-anticoagulant analogues inhibit human keratinocyte growth without inducing differentiation. J Invest Dermatol 103:647–650PubMedCrossRef Pillai S, Gilliam L, Conrad HE, Holleran WM (1994) Heparin and its non-anticoagulant analogues inhibit human keratinocyte growth without inducing differentiation. J Invest Dermatol 103:647–650PubMedCrossRef
30.
Zurück zum Zitat Ruoslahti E, Engvall E (1980) Complexing of fibronectin glycosaminoglycans and collagen. Biochim Biophys Acta 631:350–358PubMed Ruoslahti E, Engvall E (1980) Complexing of fibronectin glycosaminoglycans and collagen. Biochim Biophys Acta 631:350–358PubMed
31.
Zurück zum Zitat Schönherr E, Hausser H-J (2000) Extracellular matrix and cytokines: a functional unit. Dev Immunol 7:89–101PubMedCrossRef Schönherr E, Hausser H-J (2000) Extracellular matrix and cytokines: a functional unit. Dev Immunol 7:89–101PubMedCrossRef
32.
Zurück zum Zitat Sekiguchi K, Hakomori S, Funahashi M, Matsumoto I, Seno N (1983) Binding of fibronectin and its proteolytic fragments to glycosaminoglycans. J Biol Chem 258:14359–14365PubMed Sekiguchi K, Hakomori S, Funahashi M, Matsumoto I, Seno N (1983) Binding of fibronectin and its proteolytic fragments to glycosaminoglycans. J Biol Chem 258:14359–14365PubMed
33.
Zurück zum Zitat Shiedlin A, Bigelow R, Christopher W, Arbabi S, Yang L, Maier RV, Wainwright N, Childs A, Miller RJ (2004) Evaluation of hyaluronan from different sources: streptococcus zooepidemicus, rooster comb, bovine vitreous, and human umbilical cord. Biomacromolecules 5:2122–2127PubMedCrossRef Shiedlin A, Bigelow R, Christopher W, Arbabi S, Yang L, Maier RV, Wainwright N, Childs A, Miller RJ (2004) Evaluation of hyaluronan from different sources: streptococcus zooepidemicus, rooster comb, bovine vitreous, and human umbilical cord. Biomacromolecules 5:2122–2127PubMedCrossRef
34.
Zurück zum Zitat Specks U, Mayer U, Nischt R, Spissinger T, Mann K, Timpl R, Engel J, Chu M-L (1992) Structure of recombinant N-terminal globule of type VI collagen α3 chain and its binding to heparin and hyaluronan. EMBO J 11:4281–4290PubMed Specks U, Mayer U, Nischt R, Spissinger T, Mann K, Timpl R, Engel J, Chu M-L (1992) Structure of recombinant N-terminal globule of type VI collagen α3 chain and its binding to heparin and hyaluronan. EMBO J 11:4281–4290PubMed
35.
Zurück zum Zitat Symington FW (1989) Lymphotoxin, tumor necrosis factor, and gamma interferon are cytostatic for normal human keratinocytes. J Invest Dermatol 92:798–805PubMedCrossRef Symington FW (1989) Lymphotoxin, tumor necrosis factor, and gamma interferon are cytostatic for normal human keratinocytes. J Invest Dermatol 92:798–805PubMedCrossRef
36.
Zurück zum Zitat Tammi R, Ripellino JA, Margolis RU, Maibach HI, Tammi M (1989) Hyaluronate accumulation in human epidermis treated with retinoic acid in skin organ culture. J Invest Dermatol 92:326–332PubMedCrossRef Tammi R, Ripellino JA, Margolis RU, Maibach HI, Tammi M (1989) Hyaluronate accumulation in human epidermis treated with retinoic acid in skin organ culture. J Invest Dermatol 92:326–332PubMedCrossRef
37.
Zurück zum Zitat Tammi R, Säämänen A-M, Maibach HI, Tammi M (1991) Degradation of newly synthesized high molecular mass hyaluronan in the epidermal and dermal compartments of human skin in organ culture. J Invest Dermatol 97:126–130PubMedCrossRef Tammi R, Säämänen A-M, Maibach HI, Tammi M (1991) Degradation of newly synthesized high molecular mass hyaluronan in the epidermal and dermal compartments of human skin in organ culture. J Invest Dermatol 97:126–130PubMedCrossRef
38.
Zurück zum Zitat Tammi R, Paukkonen K, Wang C, Horsmanheimo M, Tammi M (1994) Hyaluronan and CD44 in psoriatic skin: Intense staining for hyaluronan on dermal capillary loops and reduced expression of CD44 and hyaluronan in keratinocyte-leukocyte interfaces. Arch Dermatol Res 286:21–29PubMedCrossRef Tammi R, Paukkonen K, Wang C, Horsmanheimo M, Tammi M (1994) Hyaluronan and CD44 in psoriatic skin: Intense staining for hyaluronan on dermal capillary loops and reduced expression of CD44 and hyaluronan in keratinocyte-leukocyte interfaces. Arch Dermatol Res 286:21–29PubMedCrossRef
39.
Zurück zum Zitat Tammi R, Tammi M (1991) Correlations between hyaluronan and epidermal proliferation as studied by (3H)glucosamine and (3H)thymidine incorporations and staining of hyaluronan on mitotic keratinocytes. Exp Cell Res 195:524–527PubMedCrossRef Tammi R, Tammi M (1991) Correlations between hyaluronan and epidermal proliferation as studied by (3H)glucosamine and (3H)thymidine incorporations and staining of hyaluronan on mitotic keratinocytes. Exp Cell Res 195:524–527PubMedCrossRef
40.
Zurück zum Zitat Travis JA, Hughes MG, Wong JM, Wagner WD, Geary RL (2001) Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts: role of CD44 and implications for constrictive remodeling. Circ Res 88:77–83PubMedCrossRef Travis JA, Hughes MG, Wong JM, Wagner WD, Geary RL (2001) Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts: role of CD44 and implications for constrictive remodeling. Circ Res 88:77–83PubMedCrossRef
41.
Zurück zum Zitat Valiyaveettil M, Achur RN, Alkhalil A, Ockenhouse CF, Gowda DC (2001) Plasmodium falciparum cytoadherence to human placenta: evaluation of hyaluronic acid and chondroitin 4-sulfate for binding of infected erythrocytes. Exp Parasitol 99:57–65PubMedCrossRef Valiyaveettil M, Achur RN, Alkhalil A, Ockenhouse CF, Gowda DC (2001) Plasmodium falciparum cytoadherence to human placenta: evaluation of hyaluronic acid and chondroitin 4-sulfate for binding of infected erythrocytes. Exp Parasitol 99:57–65PubMedCrossRef
42.
Zurück zum Zitat Vaughan-Thomas A, Young RD, Phillips AC, Duance VC (2001) Characterization of type XI collagen-glycosaminoglycan interactions. J Biol Chem 276:5303–5309PubMedCrossRef Vaughan-Thomas A, Young RD, Phillips AC, Duance VC (2001) Characterization of type XI collagen-glycosaminoglycan interactions. J Biol Chem 276:5303–5309PubMedCrossRef
43.
Zurück zum Zitat Yamagata M, Yamada KM, Yoneda M, Suzuki S, Kimata K (1986) Chondroitin sulfate proteoglycan (PG-M-like proteoglycan) is involved in the binding of hyaluronic acid to cellular fibronectin. J Biol Chem 261:13526–13535PubMed Yamagata M, Yamada KM, Yoneda M, Suzuki S, Kimata K (1986) Chondroitin sulfate proteoglycan (PG-M-like proteoglycan) is involved in the binding of hyaluronic acid to cellular fibronectin. J Biol Chem 261:13526–13535PubMed
44.
Zurück zum Zitat Öbrink B (1973) A study of the interactions between monomeric tropocollagen and glycosaminoglycans. Eur J Biochem 33:387–400PubMedCrossRef Öbrink B (1973) A study of the interactions between monomeric tropocollagen and glycosaminoglycans. Eur J Biochem 33:387–400PubMedCrossRef
Metadaten
Titel
Hyaluronic acid inhibits the adherence and growth of monolayer keratinocytes but does not affect the growth of keratinocyte epithelium
verfasst von
Ilkka T. Harvima
Hanna Heikura
Mika Hyttinen
Anita Naukkarinen
Publikationsdatum
01.10.2006
Verlag
Springer-Verlag
Erschienen in
Archives of Dermatological Research / Ausgabe 5/2006
Print ISSN: 0340-3696
Elektronische ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-006-0687-8

Weitere Artikel der Ausgabe 5/2006

Archives of Dermatological Research 5/2006 Zur Ausgabe

Leitlinien kompakt für die Dermatologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Hirsutismus bei PCOS: Laser- und Lichttherapien helfen

26.04.2024 Hirsutismus Nachrichten

Laser- und Lichtbehandlungen können bei Frauen mit polyzystischem Ovarialsyndrom (PCOS) den übermäßigen Haarwuchs verringern und das Wohlbefinden verbessern – bei alleiniger Anwendung oder in Kombination mit Medikamenten.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

22.04.2024 DGIM 2024 Nachrichten

Um Menschen nach der Flucht aus einem Krisengebiet bestmöglich medizinisch betreuen zu können, ist es gut zu wissen, welche Erkrankungen im jeweiligen Herkunftsland häufig sind. Dabei hilft eine Internetseite der CDC (Centers for Disease Control and Prevention).

Update Dermatologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.