Fine Regulation during Wound Healing by Mast Cells, a Physiological Role Not Yet Clarified (original) (raw)
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Mast cells and wound healing: Still an open question
Histology and Histopathology, 2025
Mast cells, which originate from the bone marrow, possess the ability to secrete a diverse array of active molecules. These molecules include mediators (histamine, heparin), which have been identified for decades and are stored in specific granules, as well as small molecules generated instantaneously in response to stimulation (membrane lipid derivatives, nitric oxide), and a multitude of multifunctional cytokines that are secreted constitutively. Activated mast cells participate in the regulation of the local immune response and exert control over critical events of inflammation and healing with the assistance of a vast array of mediators. The involvement of these cell types in inflammatory states suggests that mast cells may function as sentinels that activate local immune processes in response to various types of stimuli and the entry of antigens. Moreover, due to their proximity to nerve fibers and reactivity to a variety of neurotransmitters, mast cells are among the cells that may facilitate local neuroimmune interactions. With this in mind, it is necessary to consider their participation in the repair of injuries in both acute and chronic conditions.
The role of mast cells in wound healing
International Wound Journal, 2010
Mast cells are predominantly found in the vicinity of connective tissue vessels of skin and mucosa. The main immunological functions of mast cells are in IgE‐mediated reactions and in helminth infestations. Mast cells respond to tissue injury by releasing inflammatory mediators and have been implicated in diseases of excessive fibrosis of the dermis such as scleroderma. Current evidence suggests that mast cells exert its role during inflammation and cellular proliferation. Animal models have shown that by stabilising mast cells at the early stages of wound healing, wound contraction is reduced. Mast cells are an ideal candidate to play a pivotal role in wound healing due to its location, substances released and clinical associations.
Experimental Dermatology, 1999
Neukölln, Berlin, Germany type hypersensitivity reactions. There is, however, a growing body of evidence that the cells might play an important role in the maintenance of tissue homeostasis and repair. We here present our own data and those from the literature elucidating the possible role of mast cells during wound healing. Studies on the fate of mast cells in scars of varying ages suggest that these cells degranulate during wounding, with a marked decrease of chymase-positive cells, although the total number of cells does not decrease, based on SCF-receptor staining. Mast cells contain a plethora of preformed mediators like heparin, histamine, tryptase, chymase, VEGF and TNF-a which, on release during the initial stages of wound healing, affect bleeding and subsequent coagulation and acute inflammation. Various additional vasoactive and chemotactic, rapidly generated mediators (C3a, C5a, LTB 4 , LTC 4 , PAF) will contribute to these processes, whereas mast cell-derived proinflammatory and growth promoting peptide mediators (VEGF, FGF-2, PDGF, TGF-b, NGF, IL-4, IL-8) contribute to neoangiogenesis, fibrinogenesis or re-epithelization during the repair process. The increasing number of tryptase-positive mast cells in older Key words: mast cells -keratinocytesfibroblasts -wound healing -angiogenesis scars suggest that these cells continue to be exposed to specific chemotactic, growth-and differentiation-promoting factors throughout the pro-Prof. Dr B. M. Henz, Exp. Dermatology, cess of tissue remodelling. All these data indicate that mast cells contrib-Charité-Virchow Clinic,
Mast Cells and Angiogenesis in Wound Healing
ANALYTICAL AND QUANTITATIVE CYTOPATHOLOGY AND HISTOPATHOLOGY, 2014
Objective: To investigate the role of mast cells and vascular endothelial growth factor (VEGF) as a mediator of angiogenesis to promote wound healing in surgical and pathological scars. Study Design: The study was carried out on 40 patients who presented with active scar lesions. They were subdivided into 4 groups. They included granulation tissue (10 cases), surgical scar (10 cases), hypertrophic scar (10 cases), and keloid scar (10 cases). Also 10 healthy volunteers of the same age and sex were selected as a control group. Skin biopsies were taken from the patients and the control group. Skin biopsies from clinically assessed studied groups were processed for routine histology and embedded in paraffin. Four sections were prepared from each paraffin block. The first section was stained with hematoxylin and eosin for histological evaluation. The second and third sections were processed for immunostaining of mast cells that contain chymase (MCCs) and mast cells that contain tryptase (MCTs). The fourth section was processed for immunostaining of VEGF. Results: MCCs exhibited mild expression in normal tissue, granulation tissue, and surgical, hypertrophic and keloid scars. MCTs exhibited mild expression in normal tissue, granulation tissue and keloid, whereas moderate expression was exhibited in hypertrophic and surgical scars. VEGF expression was absent in normal tissue, mild in keloid, surgical and hypertrophic scars, and moderate in keloids and granulation tissue. Conclusion: Mast cell expression variation among different scar types signals the pathological evolution of the lesion, and hence may guide the need for therapeutic intervention.
PLoS ONE, 2013
Wound healing is a complex biological process involving the interaction of many cell types to replace lost or damaged tissue. Although the biology of wound healing has been extensively investigated, few studies have focused on the role of mast cells. In this study, we investigated the possible role of mast cells in wound healing by analyzing aspects of cutaneous excisional wound healing in three types of genetically mast cell-deficient mice. We found that C57BL/6-Kit W-sh/W-sh , WBB6F 1 -Kit W/W-v , and Cpa3-Cre; Mcl-1 fl/fl mice re-epithelialized splinted excisional skin wounds at rates very similar to those in the corresponding wild type or control mice. Furthermore, at the time of closure, scars were similar in the genetically mast celldeficient mice and the corresponding wild type or control mice in both quantity of collagen deposition and maturity of collagen fibers, as evaluated by Masson's Trichrome and Picro-Sirius red staining. These data indicate that mast cells do not play a significant non-redundant role in these features of the healing of splinted full thickness excisional cutaneous wounds in mice. (MTL) PLOS ONE | www.plosone.org
Mast Cells and Angiogenesis in Wound Healing.pdf
ANALYTICAL AND QUANTITATIVE CYTOPATHOLOGY AND HISTOPATHOLOGY, 2014
OBJECTIVE: To investigate the role of mast cells and vascular endothelial growth factor (VEGF) as a mediator of angiogenesis to promote wound healing in surgical and pathological scars. STUDY DESIGN: The study was carried out on 40 patients who presented with active scar lesions. They were subdivided into 4 groups. They included granulation tissue (10 cases), surgical scar (10 cases), hypertrophic scar (10 cases), and keloid scar (10 cases). Also 10 healthy volunteers of the same age and sex were selected as a control group. Skin biopsies were taken from the patients and the control group. Skin biopsies from clinically assessed studied groups were processed for routine histology and embedded in paraffin. Four sections were prepared from each paraffin block. The first section was stained with hernatoxylin and eosin for histological evaluation. The second and third sections were processed for immunostaining of mast cells that contain chymase (MCCs) and mast cells that contain tryptase (MCTs). The fourth section was processed for immunostaining of VEGF. RESULTS: MCCs exhibited mild expression in normal tissue, granulation tissue, and surgical, hypertrophic and keloid scars. MCTs exhibited mild expression in normal tissue, granulation tissue and keloid, whereas moderate eipression was exhibited in hypertrophic and surgical scars. VEGF expression was absent in normal tissue, mild in keloid, surgical and hypertrophic scars, and moderate in keloids and granulation tissue. CONCLUSION: Mast cell expression variation among different scar types signals the pathological evolution of the lesion, and hence may guide the need for therapeutic intervention. Keywords Author Keywords:angiogenesis; chymase; mast cells; skin tryptase; tryptase; vascular endothelial growth factor; VEGF; wound healing KeyWords Plus:ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; MONOCLONAL-ANTIBODY; SCAR FORMATION; FACTOR-BETA; TRYPTASE; EXPRESSION; MODULATE
Mast cells are required for normal healing of skin wounds in mice
The FASEB Journal, 2006
reported to play a pivotal role in the elicitation of inflammatory reactions that are beneficial to the host, e.g., during innate immune responses to bacteria. To explore whether MCs also contribute to wound repair, we studied experimentally induced skin wounds in MC-deficient Kit W /Kit W-v mice, normal Kit؉/؉ mice, and MC-reconstituted Kit W /Kit W-v mice. Wound closure was significantly impaired in the absence of MCs during the first 6 days of wound healing and histomorphometric analyses of MC degranulation at the wound edges revealed distance-dependent MC activation, i.e., MC degranulation was most prominent directly adjacent to the wound. In addition, Kit W /Kit W-v mice showed impaired extravasation and recruitment of neutrophils to the wounded areas. Notably, wound closure, extravasation, and neutrophil recruitment were found to be normal in MC-reconstituted Kit W /Kit W-v mice. Therefore, we examined whether MCs promote wound healing by releasing histamine or TNF-␣. Interestingly, wound closure was reduced in mice treated with an H 1 -receptor antagonist but not after treatment with an H 2 -receptor antagonist or in the absence of TNF-␣. Taken together, our findings indicate that MC activation and histamine release are required for normal cutaneous wound healing.-Weller, K., Foitzik, K., Paus, R., Syska, W., Maurer, M. Mast cells are required for normal healing of skin wounds in mice. FASEB J. 20, E1628 -E1635 (2006)
Plastic and Reconstructive Surgery, 2014
ast cells are immune cells that originate in the bone marrow, yet they are unique in that their differentiation and maturation occur only once they reach their target organ. 1,2 Each mast cell has on average approximately 75 granules containing a host of mediators with diverse biological roles that can be preformed or formed de novo. Some of these mediators include heparin, histamine, vascular endothelial growth factor, transforming growth factor-β, nitric oxide, chymase, elastase, and tryptase, among many others. 3 The target organ's surrounding milieu and its biological factors interact with the receptors of the immature mast cell, ultimately dictating which mediators are synthesized and stored in the mast cells' granules. 2,4,5 The diversity of the granules accounts for the involvement of mast cells in the pathophysiology of allergic reactions, inflammation, tumorigenesis, immunity, angiogenesis, and wound healing. 1,6
Mast cells as a source of multifunctional cytokines
Immunology today, 1990
Mast cells have been implicated in the expression of a wide variety of biological responses, including immediate hypersensitivity reactions, host responses to parasites and neoplasms, immunologically non-specific inflammatory and fibrotic conditions, angiogenesis, and tissue remodeling and wound healing. However, the molecular basis for the action of the mast cell in many of these responses is obscure. In this review, John Gordon, Parris Burd and Stephen Galli suggest that the production of a broad panel of multifunctional cytokines may represent an important mechanism by which mast cells influence physiological, immunological and pathological processes.