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Erschienen in: Clinical Reviews in Allergy & Immunology 3/2020

07.02.2019

A Review of the Contribution of Mast Cells in Wound Healing: Involved Molecular and Cellular Mechanisms

verfasst von: Daniel Elieh Ali Komi, Kelly Khomtchouk, Peter Luke Santa Maria

Erschienen in: Clinical Reviews in Allergy & Immunology | Ausgabe 3/2020

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Abstract

Mast cells (MCs), apart from their classic role in allergy, contribute to a number of biologic processes including wound healing. In particular, two aspects of their histologic distribution within the skin have attracted the attention of researchers to study their wound healing role; they represent up to 8% of the total number of cells within the dermis and their cutaneous versions are localized adjacent to the epidermis and the subdermal vasculature and nerves. At the onset of a cutaneous injury, the accumulation of MCs and release of proinflammatory and immunomodulatory mediators have been well documented. The role of MC-derived mediators has been investigated through the stages of wound healing including inflammation, proliferation, and remodeling. They contribute to hemostasis and clot formation by enhancing the expression of factor XIIIa in dermal dendrocytes through release of TNF-α, and contribute to clot stabilization. Keratinocytes, by secreting stem cell factor (SCF), recruit MCs to the site. MCs in return release inflammatory mediators, including predominantly histamine, VEGF, interleukin (IL)-6, and IL-8, that contribute to increase of endothelial permeability and vasodilation, and facilitate migration of inflammatory cells, mainly monocytes and neutrophils to the site of injury. MCs are capable of activating the fibroblasts and keratinocytes, the predominant cells involved in wound healing. MCs stimulate fibroblast proliferation during the proliferative phase via IL-4, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) to produce a new extracellular matrix (ECM). MC-derived mediators including fibroblast growth factor-2, VEGF, platelet-derived growth factor (PDGF), TGF-β, nerve growth factor (NGF), IL-4, and IL-8 contribute to neoangiogenesis, fibrinogenesis, or reepithelialization during the repair process. MC activation inhibition and targeting the MC-derived mediators are potential therapeutic strategies to improve wound healing through reduced inflammatory responses and scar formation.
Literatur
8.
12.
Zurück zum Zitat Martin P, D'Souza D, Martin J, Grose R, Cooper L, Maki R, McKercher SR (2003) Wound healing in the PU.1 null mouse--tissue repair is not dependent on inflammatory cells. Curr Biol: CB 13(13):1122–1128PubMedCrossRef Martin P, D'Souza D, Martin J, Grose R, Cooper L, Maki R, McKercher SR (2003) Wound healing in the PU.1 null mouse--tissue repair is not dependent on inflammatory cells. Curr Biol: CB 13(13):1122–1128PubMedCrossRef
14.
Zurück zum Zitat Artuc M, Hermes B, Steckelings UM, Grutzkau A, Henz BM (1999) Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders? Exp Dermatol 8(1):1–16CrossRefPubMed Artuc M, Hermes B, Steckelings UM, Grutzkau A, Henz BM (1999) Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders? Exp Dermatol 8(1):1–16CrossRefPubMed
22.
Zurück zum Zitat Huttunen M, Aalto ML, Harvima RJ, Horsmanheimo M, Harvima IT (2000) Alterations in mast cells showing tryptase and chymase activity in epithelializating and chronic wounds. Exp Dermatol 9(4):258–265PubMedCrossRef Huttunen M, Aalto ML, Harvima RJ, Horsmanheimo M, Harvima IT (2000) Alterations in mast cells showing tryptase and chymase activity in epithelializating and chronic wounds. Exp Dermatol 9(4):258–265PubMedCrossRef
27.
Zurück zum Zitat Hartmann K, Henz BM, Kruger-Krasagakes S, Kohl J, Burger R, Guhl S, Haase I, Lippert U, Zuberbier T (1997) C3a and C5a stimulate chemotaxis of human mast cells. Blood 89(8):2863–2870PubMedCrossRef Hartmann K, Henz BM, Kruger-Krasagakes S, Kohl J, Burger R, Guhl S, Haase I, Lippert U, Zuberbier T (1997) C3a and C5a stimulate chemotaxis of human mast cells. Blood 89(8):2863–2870PubMedCrossRef
28.
Zurück zum Zitat Wojta J, Kaun C, Zorn G, Ghannadan M, Hauswirth AW, Sperr WR, Fritsch G, Printz D, Binder BR, Schatzl G, Zwirner J, Maurer G, Huber K, Valent P (2002) C5a stimulates production of plasminogen activator inhibitor-1 in human mast cells and basophils. Blood 100(2):517–523PubMedCrossRef Wojta J, Kaun C, Zorn G, Ghannadan M, Hauswirth AW, Sperr WR, Fritsch G, Printz D, Binder BR, Schatzl G, Zwirner J, Maurer G, Huber K, Valent P (2002) C5a stimulates production of plasminogen activator inhibitor-1 in human mast cells and basophils. Blood 100(2):517–523PubMedCrossRef
31.
Zurück zum Zitat Zhu H, Liang B, Li R, Li J, Lin L, Ma S, Wang J (2013) Activation of coagulation, anti-coagulation, fibrinolysis and the complement system in patients with urticaria. Asian Pac J Allergy Immunol 31(1):43–50PubMed Zhu H, Liang B, Li R, Li J, Lin L, Ma S, Wang J (2013) Activation of coagulation, anti-coagulation, fibrinolysis and the complement system in patients with urticaria. Asian Pac J Allergy Immunol 31(1):43–50PubMed
33.
Zurück zum Zitat Gonzalo-Garijo MA, Perez-Rangel I, Alvarado-Izquierdo MI, Perez-Calderon R, Sanchez-Vega S, Zambonino MA (2010) Metrorrhagia as an uncommon symptom of anaphylaxis. J Investig Allergol Clin Immunol 20(6):540–541PubMed Gonzalo-Garijo MA, Perez-Rangel I, Alvarado-Izquierdo MI, Perez-Calderon R, Sanchez-Vega S, Zambonino MA (2010) Metrorrhagia as an uncommon symptom of anaphylaxis. J Investig Allergol Clin Immunol 20(6):540–541PubMed
36.
Zurück zum Zitat Gillitzer R, Goebeler M (2001) Chemokines in cutaneous wound healing. J Leukoc Biol 69(4):513–521PubMed Gillitzer R, Goebeler M (2001) Chemokines in cutaneous wound healing. J Leukoc Biol 69(4):513–521PubMed
40.
Zurück zum Zitat Egozi EI, Ferreira AM, Burns AL, Gamelli RL, Dipietro LA (2003) Mast cells modulate the inflammatory but not the proliferative response in healing wounds. Wound Repair Regen 11(1):46–54PubMedCrossRef Egozi EI, Ferreira AM, Burns AL, Gamelli RL, Dipietro LA (2003) Mast cells modulate the inflammatory but not the proliferative response in healing wounds. Wound Repair Regen 11(1):46–54PubMedCrossRef
45.
Zurück zum Zitat Kennelly R, Conneely JB, Bouchier-Hayes D, Winter DC (2011) Mast cells in tissue healing: from skin to the gastrointestinal tract. Curr Pharm Des 17(34):3772–3775CrossRefPubMed Kennelly R, Conneely JB, Bouchier-Hayes D, Winter DC (2011) Mast cells in tissue healing: from skin to the gastrointestinal tract. Curr Pharm Des 17(34):3772–3775CrossRefPubMed
48.
Zurück zum Zitat Soliman M, Kim DS, Park JG, Kim JY, Alfajaro MM, Baek YB, Cho EH, Park CH, Kang MI, Park SI, Cho KO (2018) PI3K/Akt and MEK/ERK signaling pathways facilitate sapovirus trafficking and late endosomal acidification for viral uncoating in LLC-PK cells. J Virol 92. https://doi.org/10.1128/jvi.01674-18 Soliman M, Kim DS, Park JG, Kim JY, Alfajaro MM, Baek YB, Cho EH, Park CH, Kang MI, Park SI, Cho KO (2018) PI3K/Akt and MEK/ERK signaling pathways facilitate sapovirus trafficking and late endosomal acidification for viral uncoating in LLC-PK cells. J Virol 92. https://​doi.​org/​10.​1128/​jvi.​01674-18
52.
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(3):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(3):184–192PubMedCrossRef
53.
Zurück zum Zitat Gruber BL (2003) Mast cells in the pathogenesis of fibrosis. Curr Rheumatol Rep 5(2):147–153PubMedCrossRef Gruber BL (2003) Mast cells in the pathogenesis of fibrosis. Curr Rheumatol Rep 5(2):147–153PubMedCrossRef
54.
Zurück zum Zitat Yamamoto T, Hartmann K, Eckes B, Krieg T (2000) Mast cells enhance contraction of three-dimensional collagen lattices by fibroblasts by cell-cell interaction: role of stem cell factor/c-kit. Immunology 99(3):435–439PubMedPubMedCentralCrossRef Yamamoto T, Hartmann K, Eckes B, Krieg T (2000) Mast cells enhance contraction of three-dimensional collagen lattices by fibroblasts by cell-cell interaction: role of stem cell factor/c-kit. Immunology 99(3):435–439PubMedPubMedCentralCrossRef
55.
Zurück zum Zitat Yamamoto T, Hartmann K, Eckes B, Krieg T (2001) Role of stem cell factor and monocyte chemoattractant protein-1 in the interaction between fibroblasts and mast cells in fibrosis. J Dermatol Sci 26(2):106–111PubMedCrossRef Yamamoto T, Hartmann K, Eckes B, Krieg T (2001) Role of stem cell factor and monocyte chemoattractant protein-1 in the interaction between fibroblasts and mast cells in fibrosis. J Dermatol Sci 26(2):106–111PubMedCrossRef
56.
Zurück zum Zitat Shiota N, Nishikori Y, Kakizoe E, Shimoura K, Niibayashi T, Shimbori C, Tanaka T, Okunishi H (2010) Pathophysiological role of skin mast cells in wound healing after scald injury: study with mast cell-deficient W/W(V) mice. Int Arch Allergy Immunol 151(1):80–88. https://doi.org/10.1159/000232573 PubMedCrossRef Shiota N, Nishikori Y, Kakizoe E, Shimoura K, Niibayashi T, Shimbori C, Tanaka T, Okunishi H (2010) Pathophysiological role of skin mast cells in wound healing after scald injury: study with mast cell-deficient W/W(V) mice. Int Arch Allergy Immunol 151(1):80–88. https://​doi.​org/​10.​1159/​000232573 PubMedCrossRef
58.
74.
Zurück zum Zitat Whitby DJ, Ferguson MW (1991) The extracellular matrix of lip wounds in fetal, neonatal and adult mice. Development 112(2):651–668PubMed Whitby DJ, Ferguson MW (1991) The extracellular matrix of lip wounds in fetal, neonatal and adult mice. Development 112(2):651–668PubMed
76.
Zurück zum Zitat Natah SS, Hayrinen-Immonen R, Hietanen J, Malmstrom M, Konttinen YT (1998) Quantitative assessment of mast cells in recurrent aphthous ulcers (RAU). J Oral Pathol Med 27(3):124–129PubMedCrossRef Natah SS, Hayrinen-Immonen R, Hietanen J, Malmstrom M, Konttinen YT (1998) Quantitative assessment of mast cells in recurrent aphthous ulcers (RAU). J Oral Pathol Med 27(3):124–129PubMedCrossRef
78.
Zurück zum Zitat Salmon-Ehr V, Ramont L, Godeau G, Birembaut P, Guenounou M, Bernard P, Maquart FX (2000) Implication of interleukin-4 in wound healing. Lab Investig 80(8):1337–1343PubMedCrossRef Salmon-Ehr V, Ramont L, Godeau G, Birembaut P, Guenounou M, Bernard P, Maquart FX (2000) Implication of interleukin-4 in wound healing. Lab Investig 80(8):1337–1343PubMedCrossRef
85.
Zurück zum Zitat Kondo S, Kagami S, Kido H, Strutz F, Muller GA, Kuroda Y (2001) Role of mast cell tryptase in renal interstitial fibrosis. J Am Soc Nephrol 12(8):1668–1676PubMed Kondo S, Kagami S, Kido H, Strutz F, Muller GA, Kuroda Y (2001) Role of mast cell tryptase in renal interstitial fibrosis. J Am Soc Nephrol 12(8):1668–1676PubMed
86.
Zurück zum Zitat Li CY, Baek JY (2002) Mastocytosis and fibrosis: role of cytokines. Int Arch Allergy Immunol 127(2):123–126PubMedCrossRef Li CY, Baek JY (2002) Mastocytosis and fibrosis: role of cytokines. Int Arch Allergy Immunol 127(2):123–126PubMedCrossRef
87.
Zurück zum Zitat Wygrecka M, Dahal BK, Kosanovic D, Petersen F, Taborski B, von Gerlach S, Didiasova M, Zakrzewicz D, Preissner KT, Schermuly RT, Markart P (2013) Mast cells and fibroblasts work in concert to aggravate pulmonary fibrosis: role of transmembrane SCF and the PAR-2/PKC-alpha/Raf-1/p44/42 signaling pathway. Am J Pathol 182(6):2094–2108. https://doi.org/10.1016/j.ajpath.2013.02.013 PubMedCrossRef Wygrecka M, Dahal BK, Kosanovic D, Petersen F, Taborski B, von Gerlach S, Didiasova M, Zakrzewicz D, Preissner KT, Schermuly RT, Markart P (2013) Mast cells and fibroblasts work in concert to aggravate pulmonary fibrosis: role of transmembrane SCF and the PAR-2/PKC-alpha/Raf-1/p44/42 signaling pathway. Am J Pathol 182(6):2094–2108. https://​doi.​org/​10.​1016/​j.​ajpath.​2013.​02.​013 PubMedCrossRef
91.
Zurück zum Zitat Iemura A, Tsai M, Ando A, Wershil BK, Galli SJ (1994) The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. Am J Pathol 144(2):321–328PubMedPubMedCentral Iemura A, Tsai M, Ando A, Wershil BK, Galli SJ (1994) The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. Am J Pathol 144(2):321–328PubMedPubMedCentral
92.
Zurück zum Zitat Alm PE, Bloom GD, Hellstrom S, Stenfors LE, Widemar L (1983) Mast cells in the pars flaccida of the tympanic membrane. A quantitative morphological and biochemical study in the rat. Experientia 39(3):287–289PubMedCrossRef Alm PE, Bloom GD, Hellstrom S, Stenfors LE, Widemar L (1983) Mast cells in the pars flaccida of the tympanic membrane. A quantitative morphological and biochemical study in the rat. Experientia 39(3):287–289PubMedCrossRef
93.
Zurück zum Zitat Widemar L, Hellstrom S, Stenfors LE, Bloom GD (1986) An overlooked site of tissue mast cells—the human tympanic membrane. Implications for middle ear affections. Acta Otolaryngol 102(5–6):391–395PubMedCrossRef Widemar L, Hellstrom S, Stenfors LE, Bloom GD (1986) An overlooked site of tissue mast cells—the human tympanic membrane. Implications for middle ear affections. Acta Otolaryngol 102(5–6):391–395PubMedCrossRef
94.
Zurück zum Zitat Ichimiya I, Kawauchi H, Mogi G (1990) Analysis of immunocompetent cells in the middle ear mucosa. Arch Otolaryngol Head Neck Surg 116(3):324–330PubMedCrossRef Ichimiya I, Kawauchi H, Mogi G (1990) Analysis of immunocompetent cells in the middle ear mucosa. Arch Otolaryngol Head Neck Surg 116(3):324–330PubMedCrossRef
95.
Zurück zum Zitat Sankovic S, Dergenc R, Bojic P (2005) Mast cells in chronic inflammation of the middle ear mucosa. Rev Laryngol Otol Rhinol 126(1):15–18 Sankovic S, Dergenc R, Bojic P (2005) Mast cells in chronic inflammation of the middle ear mucosa. Rev Laryngol Otol Rhinol 126(1):15–18
96.
Zurück zum Zitat Hurst DS, Amin K, Seveus L, Venge P (1999) Evidence of mast cell activity in the middle ears of children with otitis media with effusion. Laryngoscope 109(3):471–477PubMedCrossRef Hurst DS, Amin K, Seveus L, Venge P (1999) Evidence of mast cell activity in the middle ears of children with otitis media with effusion. Laryngoscope 109(3):471–477PubMedCrossRef
103.
107.
Zurück zum Zitat Bairy KL, Rao CM, Ramesh KV, Kulkarni DR (1991) Effects of antihistamines on wound healing. Indian J Exp Biol 29(4):398–399PubMed Bairy KL, Rao CM, Ramesh KV, Kulkarni DR (1991) Effects of antihistamines on wound healing. Indian J Exp Biol 29(4):398–399PubMed
113.
Zurück zum Zitat Younan G, Suber F, Xing W, Shi T, Kunori Y, Abrink M, Pejler G, Schlenner SM, Rodewald HR, Moore FD Jr, Stevens RL, Adachi R, Austen KF, Gurish MF (2010) The inflammatory response after an epidermal burn depends on the activities of mouse mast cell proteases 4 and 5. J Immunol 185(12):7681–7690. https://doi.org/10.4049/jimmunol.1002803 PubMedCrossRef Younan G, Suber F, Xing W, Shi T, Kunori Y, Abrink M, Pejler G, Schlenner SM, Rodewald HR, Moore FD Jr, Stevens RL, Adachi R, Austen KF, Gurish MF (2010) The inflammatory response after an epidermal burn depends on the activities of mouse mast cell proteases 4 and 5. J Immunol 185(12):7681–7690. https://​doi.​org/​10.​4049/​jimmunol.​1002803 PubMedCrossRef
Metadaten
Titel
A Review of the Contribution of Mast Cells in Wound Healing: Involved Molecular and Cellular Mechanisms
verfasst von
Daniel Elieh Ali Komi
Kelly Khomtchouk
Peter Luke Santa Maria
Publikationsdatum
07.02.2019
Verlag
Springer US
Erschienen in
Clinical Reviews in Allergy & Immunology / Ausgabe 3/2020
Print ISSN: 1080-0549
Elektronische ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-019-08729-w

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