Increased tissue survival in experimental skin flaps in mast cell-deficient rats (original) (raw)

The role of mast cell-derived histamine in the closure of an in vitro wound

Inflammation Research, 1996

We have previously reported that mast cells (MC) stimulate 3T3 fibroblast migration and proliferation into an in vitro model of wound obtained by producing in a confluent 3T3 monolayer, a midline cut and by scraping the cells from half of the monolayer. The purpose of the present study was to determine the contribution of mast cell-derived histamine to this MC increasing effect. Histamine levels in supernatants of MC/ 3T3 cultures unactivated or activated with either compound 48/80 or anti-IgE antibodies (10 rain) did not correlate to the degree of fibroblast migration and proliferation into the wound space (42h). Various concentrations of histamine were added to 3T3 fibroblast monolayers in the absence of cocultured MC, and fibroblasts beyond the wound line were counted (42 h). Addition of 100ng/ml histamine had the highest stimulating effect on fibroblast numbers. This effect was abrogated by the addition of cimetidine (an H-2 antagonist). Addition of cimetidine to unactivated MC/ 3T3 cultures did not affect the increasing activity of MC presence on the wounded monolayer, although it diminished the enhancing effect obtained after MC activation with compound 48/80. These results indicate that histamine is partially responsible for the mast cell enhancing effect on fibroblast migration and proliferation in an in vitro model of wound.

Evidence of mast-cell histamine being mitogenic in intact tissue

Agents and Actions, 1985

In cultured rat mesentery there was a spontaneous release of about 45% of the histamine in 2 days, and a spontaneous marked increase in basal proliferation of the mesentery. The MC secretagogues, compound 48/80 and polymyxin B, released additional histamine and stimulated mitogenesis further. In contrast, 48/80 added to cultures of guinea-pig mesentery, the MC of which are unresponsive to the drug, did not affect the basal proliferation. However, exogenous histamine at 10 10 Mmitogenlcally stimulated the cultured guinea-pig mesentery. A histamine H2-reeeptor antagonist, which itself was mitogenieaUy inert, significantly suppressed the 48/80-1nduced MC-mediated mitogenesis in rat mesentery in vDo and in vitro. On the other hand, a histamine Hi-receptor antagonist did not affect this MCmediated mitogenesis in rat.

Mast cells and their mediators in cutaneous wound healing ? active participants or innocent bystanders?

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,

Histamine content and mast cell numbers in tissues of normal and athymic rats

Agents and Actions, 1986

Tissue histamine levels and mast cell numbers were determined in the skin, tongue and jejunum of female rnu/nu and rnn/+ rats aged between 5 and 29 weeks. The tongue and jejunal mucosa of rnn/nu rats had a larger mast cell density and histamine content than rnu/+. There was a marked increase in subepithelial mast cells in the skin of rnu/nu rats compared with their normal littermates, while mast cell numbers in the deep skin layer and the histamine content were similar in the two groups of rat. Subepithelial skin mast cells were smaller, of more variable shape and contained fewer granules than mast cells in the deep dermal layer, and, unlike the latter, did not emi t a yellow fluorescence after treatment with o-phthalaldehyde. The results indicate that the bulk of the skin histamine is contained in mast cells residing in deep skin layers. They also support the view that the thymus may have a suppressive effect on both mucosai and connective tissue mast cells in vivo.

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.

Histamine iontophoresis on the viability of random skin flap in rats

Acta Cirurgica Brasileira, 2009

To evaluate the effects of the histamine iontophoresis on the random skin flap viability in rats. Methods: Sixty adult male Wistar rats were used. A cranially-based dorsal skin flap measuring 10 x 4 cm was raised and a plastic barrier was placed between the flap and its bed. After the surgical procedure, the animals were randomized into four groups (G1-G4) (n=15 each group) as follows: G1 (control)-sham electrical stimulation, G2 (electrical stimulation)-direct current electrical stimulation, G3 (histamine)-histamine and sham electrical stimulation and G4 (histamine iontophoresis)-transdermal iontophoresis of histamine. In all groups the procedures were performed immediately after the surgery and on the two subsequent days. The percentage of flap necrosis was measured on the seventh postoperative day. Results: The mean and the respective standard deviation of the percentage of flap necrosis areas were as follows: G1 (control)-47.87 ± 9.13%, G2-51.49 ± 8.19%, G3-46.33 ± 8.32% and G4-30.82 ± 11.25%. The G4 group presented a significantly smaller amount of flap necrosis when compared to the other groups (p<0.001). Conclusion: The topical administration of the histamine by iontophoresis was effective to increase the viability of the random skin flaps in rats.

Local Mitogenic Effect of Tissue Mast Cell Secretion

Cell Proliferation, 1980

The effect of drug-induced mast cell secretion on proliferation .was studied in fibroblast-like and mesothelial-like cells in organ-cultured rat mesentery. Mast cell degranulation achieved by Compound 48/80 was followed by a marked mitogenic reaction in the surrounding tissue cells. The drug itself lacked mitogenic effect on cultured guinea-pig mesentery, the mast cells of which are unresponsive to the drug, and on a human normal fibroblast-like cell line. In contrast, histamine at about lo-'' M, a major mast cell component, induced marked mitogenesis in guinea-pig mesentery without causing degranulation of mast cells.

Skin Mast Cell Promotion in Random Skin Flaps in Rats using Bone Marrow Mesenchymal Stem Cells and Amniotic Membrane

Iranian biomedical journal, 2018

Skin flap procedures are employed in plastic surgery, but failure can lead to necrosis of the flap. Studies have used bone marrow mesenchymal stem cells (BM-MSCs) to improve flap viability. BM-MSCs and acellular amniotic membrane (AAM) have been introduced as alternatives. The objective of this study was to evaluate the effect of BM-MSCs and AAM on mast cells of random skin flaps (RSF) in rats. RSFs (80 × 30 mm) were created on 40 rats that were randomly assigned to one of four groups, including (I) AAM, (II) BM-MSCs, (III) BM-MSCs/AAM, and (IV) saline (control). Transplantation was carried out during the procedure (zero day). Flap necrosis was observed on day 7, and skin samples were collected from the transition line of the flap to evaluate the total number and types of mast cells. The development and the total number of mast cells were related to the development of capillaries. The results of one-way ANOVA indicated that there was no statistically significant difference between t...

Histological Evaluation of Different Types of Mastocytes in the Skin Flap Using Bone Marrow Mesenchymal Stem Cells Through Biological Growth Factor

Journal of Babol University of Medical Sciences, 2018

J Babol Univ Med Sci; 20(3); Mar 2018; PP: 21-8 Received: Sep 26 2017, Revised: Dec 9 2017, Accepted: Jan 9 2018. ABSTRACT BACKGROUND AND OBJECTIVE: Skin flap is one of the most commonly used methods in plastic surgery. Postoperative skin flap necrosis is one of the complications of flap skin. The aim of this study was to evaluate the effect of bone marrow mesenchymal stem cells (BM-MSCs) and chick embryo extract (CEE) on mast cells in a randomized skin flap in rats. METHODS: In this experimental study, 40 male albino Wistar rats weighing 250 – 300 g were divided into four groups of 10 (control, CEE/BM-MSCs, CEE and BM-MSCs). Skin flap (30 × 80 mm) was created behind the animals. Surgery was performed on day zero and therapeutic intervention was done on the same day. Mesenchymal stem cells were extracted from rat bone marrow and were injected. CEE was prepared from a 9-day-old embryo of Marandi chicken. On the seventh day after the surgery, samples were assessed in term of type, and...

Evidence That Mast Cells Are Not Required for Healing of Splinted Cutaneous Excisional Wounds in Mice

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