金黄色葡萄球菌致皮肤脓肿中肥大细胞的活化
Research in Veterinary Science兽医科学研究
Activation of mast cells in skin abscess induced by Staphylococcus aureus (S.aureus) infection in mice Zhiqiang Leia,b,c,1, Ding Zhangd,1, Boyong Lue, Wenjiang Zhouf, Decheng Wanga,b,?a Medical College of China Three Gorges University, Yichang, 443002, China b The Institute of Infection and Inflammation, China Three Gorges University, Yichang 443002, Hubei, China c Wuxue First People's Hospital, Wuxue 435400, Hubei, China
d Department of Pathology, Yichang Central People's Hospital, Yichang 443003, Hubei, China
e The Third Hospital o
f Yichan
g City, Yichang 443003, Hubei, China
f Shanghai Public Health Clinical Center, Public Health Clinical Center Affiliated to Fudan University, Shanghai 201508, China 金黄色葡萄球菌致皮肤脓肿中肥大细胞的活化（S）
金黄色葡萄球菌感染小鼠
支强磊阿，B，C，1，Ding Zhangd，1，薄永璐锷，温江周夫，Decheng Wanga，B，
三峡大学仁和医院医学院，中国宜昌443002三峡大学仁和医院感染与炎症研究所，中国湖北宜昌443002
武穴市第一人民医院，武穴，湖北，中国，435400
宜昌市中心人民医院病理区，中国湖北宜昌443003
E宜昌市宜昌第三医院，中国湖北443003
复旦大学公共卫生临床中心上海公共卫生临床中心，中国上海201508
The skin abscess is a common inflammatory disease that occurs following the ubiquitous S. aureus infection. In
our study, a skin abscess murine model was established and the dynamics of mast cells chemotaxing was evaluated. In the S. aureus-infected mice, severe infiltration of inflammatory cells in the dermis were observed,
and mast cells were markedly accumulated in the skins. Besides, tryptase, the marker for mast cells activation,
has a positive correlation with mast cell activity. The mast cells identified in the tissues were likely to be
activated since they were associated with cell degranulation and the presence of tryptase. Our
results suggested,that mast cells and its mediator tryptase contribute to the inflammation of skin abscess induced by S. aureus
infection.皮肤脓肿是普遍存在的金黄色葡萄球菌感染后发生的一种常见的炎症性疾病。在
本研究建立了小鼠皮肤脓肿模型，并对肥大细胞的化学动力学进行了研究。
评价的。在金黄色葡萄球菌感染的小鼠中，观察到真皮中炎性细胞的严重浸润，
肥大细胞在皮肤中明显积累。此外，胰蛋白酶是肥大细胞活化的标志物，
与肥大细胞活性呈正相关。组织中鉴定的肥大细胞很可能是
活化，因为它们与细胞脱颗粒和存在的类胰蛋白酶。我们的结果表明
肥大细胞及其介导的类胰蛋白酶参与金黄色葡萄球菌引起的皮肤脓肿的炎症反应
感染。
金黄色葡萄球菌致皮肤脓肿中肥大细胞的活化（S）金黄色葡萄球菌感染小鼠
Skin abscesses are fairly common which usually occur
in an infection both on the skin surface and within the deeper structures. An abscess may develop and enlarge, depending on whether microorganisms
or leukocytes gain the upper hand in any one of a number of locations
in the body (Tinelli et al., 2009). Abscess tends to get worse as time goes
on, while it can spread to deeper tissues, and even enters the bloodstream to affect other organs, such as brain, liver, lungs, teeth, and
tonsils(Amir et al., 2010). Skin abscess are commonly caused by infectious pathogen, such as the ubiquitous Staphylococcus aureus (S.
aureus) bacteria (Chambers, 2001; Lowy, 1998). During the past
20 years, an dramatically increasing staphylococcal infections incidence and antibiotic resistance have posed severe burden to human
health, in which a notable strain is called
methicillin-resistant Staphylococcus aureus (MRSA) (Cardo et al., 2002; Grundmann et al., 2006;
Lowy, 1998)皮肤脓肿是常见的，通常发生在皮肤表面和深层结构内的感染。脓肿可能发展和扩大，取决于是否有微生物。
或白细胞在许多位置中的任何一个占优势。在体内（Tinelli等人，2009）。脓肿往往随着时间的流逝而变得更坏。
当它可以扩散到更深的组织，甚至进入血流以影响其他器官，如大脑、肝脏、肺、牙齿，以及
扁桃体（阿米尔等，2010）。皮肤脓肿通常是由感染性病原体引起的，如普遍存在的金黄色葡萄球菌（S）。
金黄色葡萄球菌（室，2001；洛伊，1998）。在过去
20年来，葡萄球菌感染的发病率和耐药性急剧增加，给人类带来了沉重的负担。
健康方面，其中显著菌株被称为耐甲氧西林金黄色葡萄球菌(MRSA)(Cardo等人，2002；Grundmann等人，2006)；
洛伊，1998）
Mast cells which are main effector cells of inflammation, resident in
tissues throughout the body and is abundant in the boundaries between
the outside and internal world, such as the skin, mucosa of the respiratory and digestive tract (Galli et al., 2005; Metcalfe et al., 1997).
Mast cells play a pivotal role in the inflammatory process. Underactivation, they rapidly release its typical granules and various hormonal mediators into the interstitium, such as tryptase, histamine and5-HT to exert multiple actions in the tissue microenvironments (Galli
et al., 1999; Marshall, 2004; Wang et al., 2008). It demonstrated that
mast cells can be activated after infection with RSV or cytomegalovirus
in bovine and rodent models (Gibbons et al., 1990; van Schaik et al.,
1999). Others have demonstrated that mast cells perform a positive role
in viral invasion by dodging immunosurveillance and aggravating the
inflammatory responses (King et al., 2000; Wang et al., 2008). These
findings strongly suggest the importance of mast cells in the interplay
between pathogens and their contribution in the induction of acute
inflammation response 肥大细胞是炎症的主要效应细胞，驻留在
组织遍及全身，并有丰富的界限。
外部和内部世界，例如皮肤、呼吸道和消化道的粘膜(Galli等人，2005；Metcalfe等人，1997)。
肥大细胞在炎症过程中起着关键性的作用。在激活不足时，它们迅速将其典型颗粒和各种激素介质释放到间质中，如类胰蛋白酶、组胺和5-HT，从而在组织微环境中发挥多种作用(Galli
等人，1999；马歇尔，2004；王等人，2008）。它证明了
肥大细胞可在呼吸道合胞病毒或巨细胞病毒感染后激活
在牛和啮齿动物模型中（吉本斯等人，1990；van Schaik等人，
1999）。其他已经证明肥大细胞发挥了积极的作用。
通过逃避免疫监视而加重病毒入侵
炎性反应（King等人，2000；王等人，2008）。这些
Bacterial skin infections cause different outcome, such as wound
infection, atomic dermatitis (AD), abscess, staphylococcal scalded skin
syndrome, which is from minor annoying to deadly. However, S. aureus
is notably and responsible for most skin inflammatory diseases, especially the increasing emergence of MRSA (Chambers, 2008; Hammond
and Baden, 2008). Because of its profound impact on human and animal health, the investigations of S. aureus-infection are greatly appeals
to biomedical community (Fournier and Philpott, 2005). However, few
data were collected to delineate the kinetics of mast cells in skin abscess
induced by S. aureus infection. In our study, we generated a skin abscessmouse model by administrating a clinical isolated S. aureus strain, and
evaluated the mast cell attracting and tryptase
activity in the skin inflammatory response. In addition, we quantified the dynamics of mast
cell and tryptase during the MRSA infection. This study may help us to
reveal the underlying mechanism in skin abscess caused by S. aureus
infection 细菌性皮肤感染会导致不同的结果，例如伤口。
感染，atomic dermatitis（AD），脓肿，葡萄球菌烫伤样皮肤
综合征，从轻微恼人到致命。然而，S. aureus
是大多数皮肤炎症性疾病，特别是MRSA发病率增加的主要原因（Chambers，2008；Hammond）
和Baden，2008）。由于其对人类和动物健康的深远影响，金黄色葡萄球菌感染的研究受到极大的关注。
生物医学社区（福尼尔和Philpott，2005）。然而，很少
收集皮肤脓肿肥大细胞的动力学数据。
金黄色葡萄球菌感染诱导。在我们的研究中，我们通过临床分离的金黄色葡萄球菌菌株产生了皮肤脓肿小鼠模型，
评价肥大细胞吸引和胰蛋白酶活性在皮肤炎症反应中的作用。此外，我们还对桅杆的动力学进行了量化。
MRSA感染过程中的细胞和类胰蛋白酶。这项研究可能有助于我们
金黄色葡萄球菌致皮肤脓肿的机制探讨
感染”
2. Materials and methods2。材料与方法2.1. Bacterial strains 2.1。细菌菌株
S. aureus ST-239, a prevalent clinical strain isolate, identified and
characterized by Shanghai Huashan Hospital (Li et al., 2009), was used
in this study. Firstly, S. aureus ST-239 was grown to mid-exponential
phase in tryptone-soya broth (TSB, Oxoid Ltd., Basingtoke, Hampshire,
England), and washed once with sterile phosphate buffered-saline
(PBS), then resuspended in PBS at 5 × 108 CFUs/50 μl for skin abscess
model 金黄色葡萄球菌ST-249是一种流行的临床分离株
以上海华山医院为特征（李等，2009）。
在这项研究中。首先，金黄色葡萄球菌ST-23 9生长至指数中期。
胰蛋白胨大豆肉汤中的阶段（TSB，OxoD有限公司，巴辛托克，汉普郡）
英国），用无菌磷酸盐缓冲盐水冲洗一次。（PBS）在5×108 CFU/50μl的PBS中再悬浮于皮肤脓肿中。
模型
Animals and skin abscess model动物皮肤脓肿模型
For the skin abscess model, thirty five-week-old (15-to 20-g),
inbred, special-pathogen-free, BALB/c nude mice (SINO-British SIPPR/
BK. Lab.Animal. Ltd., Shanghai, China) were used in this experiment.
They were divided randomly into two groups: 10 mice as the controls,
and 20 mice in the ST-239 infected group. Mice were anesthetized with
isoflurane and inoculated with 50 μl PBS containing 5× 108 live S.
aureus or sterile PBS in the right flank by subcutaneous injection. We
examined animals at 24-hour intervals for a total of 10 days with a
caliper, the skin lesions value was calculated with the formula L × W
(L—length, W—width). All animals were examined and weighed serially by a blinded observer. Animal infection experiments were performed at the Animal Center of Shanghai Public Health Clinical Center,
and approved by the Animal Care and Use Committee of Public Health
Clinical Center Affiliated to Fudan University.对于皮肤脓肿模型，三十五周龄（15～
20g），
近交、无特殊病原体、BALB/c裸鼠（中英SIPRP/）
B.L.动物。本实验采用的是中国上海有限公司。
随机分为两组：10只小鼠作为对照组，
ST-23 9感染组小鼠20只。小鼠麻醉
异氟醚接种50μL PBS，含有5×108的活菌。右侧皮下注射金黄色葡萄球菌或无菌性PBS。我们
以24小时为间隔的实验动物，共10天
用公式L×W计算皮肤损伤值
（L长，W宽）。所有动物都被盲人观察并连续称重。动物感染实验在上海公共卫生临床中心动物中心进行，
经动物卫生和公共卫生使用委员会批准
复旦大学附属临床中心。
Animals were weighed immediately prior to inoculation, thereafter,
animals were observed at 24-hour intervals after inoculation for a total
of 10 days. Lesions were measured with a caliper. Abscess size was
calculated by using the formula for a spherical ellipsoid [V = (π/6)
L.W2], where L is length and W is width. Areas were calculated for
dermonecrosis by using the formula A = π (L.W)/2. Lesion sizes were
recorded by day of observation and graphed. For each animal, the area
under the lesion size curve (lesion volume) was determined and used as
a measure of disease 动物在接种前立即称重，
在接种后24小时内观察动物总数。
10天。病变用测径仪测量。脓肿大小为
用球面椭球公式计算[V=（π/ 6）]
L.W2]，其中L为长度，W为宽度。计算面积使用公式a=π（Lw）/ 2的皮肤坏死。病灶大小为
通过观察和记录的日期记录。对于每一个动物，该地区
根据病变大小曲线（病灶体积）确定并使用疾病的量度
On days 1, 2, 3, … 9 and 10 post-infection, one animal from each
group were selected randomly and killed, and the skin tissue around the
injection sites were collected. The sample of each skin tissue was fixed
immediately by immersion in 2.5% (v/v) glutaraldehyde-polyoxymethylene solution and then kept at room temperature for 72 h
until used for sections preparation 感染后第1, 2, 3天，第9天和第10天，每只动物一只。
随机分组并处死，周围皮肤组织
收集注射部位。每个皮肤组织样本固定。
立即浸泡在2.5%（V/V）戊二醛聚甲醛溶液中，然后在室温下保持72小时。
直到用于切片准备
2.5. Skin histopathology 2.5。皮肤组织病理学
In order to characterize the histopathology of the mice, biopsy
specimens were taken after the following treatments. For histological
studies, the fixed skin tissues were dehydrated by increasing concentrations of ethanol, and the tissues were embedded in paraffin.
Thereafter, sections of tissue were cut at 5 μm, mounted on clean glass
slides, and dried overnight at 37 °C. Sections were cleared, hydrated,
and stained with hematoxylin-eosin solution for histological damage evaluation, according to the standard protocol of our lab, and the slides
were coded to prevent observer bias during evaluation. All tissue sections were examined with an Motic microscope (Motic China Group Co.
Ltd., Xiamen, China).为了表征小鼠的组织病理学，活检。
在后续处理后取标本。组织学
研究发现，固定皮肤组织通过增加乙醇浓度脱水，组织被石蜡包埋。
然后将切片切成5μm，安装在干净的玻璃上。幻灯片，并在37°C干燥过夜，切片，水合，用苏木精-伊红染色组织学损伤评价，按照本实验室标准方案，并制作切片。
在评估期间被编码以防止观察者偏倚。所有组织切片均采用MODIC显微镜（MOTIC中国集团）进行检测。
中国厦门有限公司。
2.6. Distribution of mast cells by improved toluidine blue staining 2.6。改良甲苯胺蓝染色法测定肥大细胞的分布
Mast cells were identified by an improved toluidine blue staining
method according to previous reports (Wang et al., 2008). Briefly,
tissue samples were dehydrated, embedded in paraffin, deparaffinized,
rehydrated, and immersed in 0.8% toluidine blue (Sigma Co.) for 15 s.
Slides were next washed with distilled water for 30 s, immediately
placed into 95% alcohol until the mast cells appeared deep reddish
purple under the microscope, immersed for 3 min successively in 100%
alcohol, alcohol-xylol (1/1, v/v), and xylol, and then mounted with
neutral gums.改良甲苯胺蓝染色法鉴定肥大细胞
方法根据以前的报告（王等人，2008）。简要地，
组织标本脱水，石蜡包埋，脱甲，
再水合，浸入0.8%甲苯胺蓝（Sigma公司）15秒。
接着用蒸馏水将玻片冲洗30秒。
放入95%酒精直至肥大细胞出现深红色。
在显微镜下浸泡3分钟，连续浸泡100%分钟。乙醇，醇二甲苯（1/1，V/V），和二甲苯，然后装上。
中性牙龈
Quantitative analysis of mast cell density in skin samples were
performed by counting the number of mast cells in 10 high-power fields
(40 × magnification), and the mean was calculated. The whole section
was scanned for general qualitative observations, but detailed examination focused on mast cells. Sampling of the sections was unbiased,
with the samples coded and examinations performed by one investigator. Mast cell density was expressed as cells per square millimeter 皮肤标本肥大细胞密度的定量分析
通过计算10个高功率场中肥大细胞的数目（40×放大），计算平均值。整段
扫描一般定性观察，但详细检查侧重于肥大细胞。截面的取样是无偏的，
由一名调查人员进行编码和检查。肥大细胞密度表示为每平方毫米细胞。
2.7. Measurement of mast cell-associated mediators tryptase with
immunohistochemical staining 2.7。肥大细胞相关介质类胰蛋白酶的测定免疫组织化学染色
Tryptase is synthesized almost exclusively by mast cells, being released after mast cell degranulation and, because it is stored almost
exclusively in mast cells, this mediator has attracted particular attention as a marker for mast cells activation in this study (Feng et al.,
2007). Examinations of tryptase in tissue samples were performed by
immunohistochemical analyses, based on previous report (Buffa et al.,
1980), and tryptase positives in skin samples counted by Leica Qwin
image soft (Leica Co. Ltd., Germany) and recorded as the percentage of
tryptase positives per total 胰蛋白酶几乎完全由肥大细胞合成，在肥大细胞脱颗粒后释放，因为它几乎被储存。
仅在肥大细胞中，这种介质作为肥大细胞活化的标志物在本研究中引起了特别关注(Feng 等，
2007）。对组织标本中的类胰蛋白酶进行检测。
免疫组化分析，基于以前的报告（Buffa等，1980）和徕卡QWIN计数的皮肤样品中的类胰蛋白酶阳性
图像软（徕卡有限公司，德国），并记录为百分比
总胰蛋白酶活性
2.8. Statistical analysis 2.8。统计分析
Lesion volumes were calculated and data were analyzed with
Microsoft Excel Statistical Software t-test for normally distributed data
with equal variances. The results were expressed as means and standard
errors. Differences were considered significant at p < 0.05 or
p < 0.01.计算病灶体积，并进行数据分析。
正态分布数据的微软Excel统计软件T检验方差相等。结果表示为手段和标准。
错误。差异有显著性（P＜0.05）。
P＜0.01。
3.1. Clinical and gross observation of skin abscess 3.1。皮肤脓肿的临床及大体观察
The skin of S. aureus-infected mice developed visible changes of
abscess signs, such as redness and edema at the early stage of infection,
and ulcer and drain at the later phase (Fig. 1A,B). Importantly, the skin
abscess volume in S. aureus-infected mice were significantly larger than
those of sterile PBS control group (Fig. 1C). Skin abscess became erythematous and fluctuant by day 3 to 4. These lesions progressed to 7 to
15 mm in diameter over 5 to 7 days, and then drained externally
through the overlying epidermis (Fig. 1C).金黄色葡萄球菌感染小鼠的皮肤出现了明显的变化。
脓肿征象，如感染初期红肿水肿，
溃疡和引流在后期（图1A，B）。重要的是，皮肤
金黄色葡萄球菌感染小鼠脓肿体积显著大于无菌PBBS对照组（图1C）。皮肤脓肿在第3天到第4天变成红斑和波动。这些病变进展到7。15毫米直径超过5至7天，然后外部排水。
通过覆盖的表皮（图1C）。
Skin histopathology examination
Severe inflammatory responses were observed in the S. aureus-infected mice under microscope, the epidermis were thicker compared
with the control mice at the early infection stage (Fig. 1G). The epidermic basal lamina were thickened and the cell components were
gradually vanished (Fig. 1G,H). The dermic collagen fiber and other 金黄色葡萄球菌感染小鼠在显微镜下观察到严重的炎症反应，表皮较厚。
对照组小鼠处于早期感染阶段（图1g）。表皮基底层增厚，细胞成分增多。
逐渐消失（图1G，H）。真皮胶原纤维及其他
Fig. 1. Variation of skin abscess and histopathology of mice after S. aureus infection. (A),(B) and (C), Gross observation of skin abscess between PBS and S. aureus infected mice. Visible
skin abscess were formed in the mice after injected subcutaneously with ST-239 S. aureus, however, asymptomatic skin in the control mice. (C), Dynamics of skin abscess volume in PBS
and S. aureus-infected mice. (D-I). Histopathology of BALB/c nude mice skin at days 1, 5 and 7 after PBS and S. aureus treatment. D, E and F, normal skin structures in PBS-treated mice.
Fewer inflammatory cells were infiltrated in epidermis and dermis, the collagen and elastic fibers were distributed normally within the dermis. G, H and I, severe inflammatory injury in
the skin after S. aureus infection. G. cellular hyperplasia obviously formed in the epidermis. H, The dermic collagen and elastic fibers were fractured and replaced by numerous inflammatory cells, the epidermic cell layers were thinning gradually. I, Transparent cornification in epidermis and infiltration of inflammatory cells within hypodermis (D, ×40, E,
×160; FeI, ×200). The abscess volume of S. aureus infected mice are obvious larger than those in the PBS treated mice, the “**” indicates significant difference from the PBS group at
p < 0.01.图1。金黄色葡萄球菌感染小鼠皮肤脓肿及组织病理学变化（a）、（b）和（c）大体观察PBS和金黄色葡萄球菌感染小鼠皮肤脓肿。可见的
小鼠皮下注射ST-239金黄色葡萄球菌后出现皮肤脓肿，而对照组无症状。（c）PBS皮肤脓肿体积的动态变化
金黄色葡萄球菌感染小鼠。（D-Ⅰ）。PBS和金黄色葡萄球菌治疗后第1, 5天和第7天BALB/c裸鼠皮肤组织病理学观察D，E和F，PBS 处理小鼠的正常皮肤结构。
表皮和真皮中炎性细胞浸润较少，真皮内胶原和弹性纤维分布正常。G，H和I，严重炎性损伤
金黄色葡萄球菌感染后的皮肤。细胞增生明显在表皮形成。h，真皮胶原纤维和弹性纤维断裂并被大量替换。
炎性细胞，表皮细胞层逐渐变薄。I，表皮透明角质化，皮下炎细胞浸润（D，×40，E，×160；费，×200）。金黄色葡萄球菌感染小鼠的脓肿体积明显大于PBS处理组，在
P＜0.01。
fibrious structures were disrupted, disappeared and infiltrated with
numerous inflammatory cells (Fig. 1G, H and I). However, there were
normal distribution and composition of skin epidermic and dermic in
the PBS control group (Fig. 1D–F).纤维性结构被破坏、消失和浸润。
大量炎性细胞（图1G，H和I）。然而，有皮肤表皮和真皮的正常分布和组成
PBS对照组（图1D～F）。
3.3. Distribution and variation of mast cells 3.3。肥大细胞的分布与变异
Mast cells were recognized as round or elongated cells in tissues and
usually identified by toluidine blue staining procedure (Humanson,infected groups (p < 0.01, Fig.
2G). Overall, the number of mast cells
was dramatically greater in the S. aureus-infected group as compared to
the control (p < 0.01, Fig. 2G), the morphology of mast cells changed
over the course of the infection. Mast cells in the control group were
almost intact (Fig. 2A–C)肥大细胞被认为是组织中的圆形或伸长细胞。通常采用甲苯胺蓝染色法（Houthon染色法），感染组（P＜0.01，图2G）。总的来说，肥大细胞的数量。
金黄色葡萄球菌感染组与对照组相比明显更大。
对照组（P＜0.01，图2G），肥大细胞形态改变。
在感染过程中。对照组肥大细胞分别为
几乎完好无损（图2A～C）
3.4. Expression and distribution of Tryptase 3.4。类胰蛋白酶的表达与分布
Considering the tryptase as one of the most important granule released by activated mast cells, the expression and distribution of serotonin was examined (Buffa et al., 1980). Tryptase positive indications were observed extensively in the infected mice, which is mostly distributed in the dermic and the sites closed to abscess, while tryptase
were scarcely detected from the controls (Fig. 3A,B). Besides, tryptase
significantly increased from day 1 to 10 post-infection in infected animals compared with the controls (p < 0.01, Fig. 3C). Furthermore,
tryptase expression was positively correlated with mast cell distribution
under microscope 考虑到类胰蛋白酶是活化肥大细胞释放的最重要的颗粒之一，我们检测了5-羟色胺的表达和分布(Buffa等人，1980)。类胰蛋白酶阳性征象
在感染小鼠中广泛观察到，主要分布在皮肤和脓肿附近，而类胰蛋白酶
对照组几乎未检测到（图3A、B）。除此之外，类胰蛋白酶
与对照组相比，感染后第1天至第10天的感染率显著升高（P＜0.01，图3C）。此外，
类胰蛋白酶表达与肥大细胞分布呈正相关
显微镜下
4. Discussion4。讨论
Skin infections are increasingly prevalent clinical problems, either
occurs on the skin surface or within the deeper. Most abscesses are
caused by S. aureus bacteria (see Bacterial Infections: Staphylococcus
aureus Infections), especially in a weakened immune system, obesity,
old age, and possibly diabetes status (Cardo et al., 2002; Kuklin et al.,
2006). The emergence and spread of MRSA is an increasing publichealth threat over the world (Chambers, 2001; Grundmann et al., 2006;
Lowy, 1998). Thus, there is a pressing need for the development of
novel therapeutic strategies against this important pathogen. In this
study, we established a solid mouse skin abscess model using an isolated S. aureus strain, and subsequently evaluate the dynamics of mast
cell chemotaxis during this process. Transparent skin disorders and
solid abscess formation were observed in the S. aureus-infected mice.
Moreover, severe inflammatory cells infiltration and fibers disruption
were observed in the dermis of S. aureus-infected mice. Furthermore,
numerous mast cells and serotonin were obviously distributed around
the abscess in the S. aureus-infected animals 皮肤感染是越来越普遍的临床问题。
发生在皮肤表面或更深。大多数脓肿是
金黄色葡萄球菌引起的细菌感染：葡萄球菌金黄色葡萄球菌感染，特别是在免疫力低下的情况下，肥胖，
老年，可能糖尿病状态（CARDO等，2002；KukLin等，
2006）。MRSA的出现和传播是世界范围内日益增加的公共健康威胁（室，2001；Grand曼等人，2006；
洛伊，1998）。因此，迫切需要发展。
针对这一重要病原体的新治疗策略。在这
研究中，我们利用分离的金黄色葡萄球菌建立小鼠皮肤脓肿模型，并随后评估桅杆的动态。细胞在这一过程中趋化。透明皮肤病
在金黄色葡萄球菌感染的小鼠中观察到固体脓肿形成。
此外，严重的炎性细胞浸润和纤维断裂。
在金黄色葡萄球菌感染小鼠的真皮中观察。此外，
大量肥大细胞和5-羟色胺明显分布在周围。金黄色葡萄球菌感染的脓肿
Mast cells were regarded as an abundant resident guard to monitor
the outside invader (Marshall, 2004). They can be activated immediately and release numerous mediators when confront or encountered the pathogens. The released bioactive molecules not only
participate in the local inflammatory responses directly, but also act as
initiators of optimal acquired immunity against pathogens (Galli et al.,
2005; Marshall, 2004). In our study, we observed increased mast cellsaccumulation in the skins of S. aureus-infected mice, both in the epidermis and dermis. While in the control mice, few mast cell was detected in the same sites, indicating that mast cells are activated over the
course of S. aureus infection. Tryptase, a mediator released by activated
mast cell was quantified, and results showed that marked increasing
and extensive distribution in the epidermis and dermis of S. aureusinfected mice, whereas tryptase scarcely expressed in the control animals. Moreover, our data collected from microscopic observation suggests that those activated mast cells may play an important role in the
inflammatory process induced by S. aureus. This correlation consisted
with a previous study which documented the importance of mast cells
in Dengue virus infection (King et al., 2000). Although the results indicated that mast cells and tryptase have implicated the various stages
of skin abscess, it is still unclear whether the other mediators released
by mast cells contribute to this disease 肥大细胞被认为是一个丰富的居民监护人。外来侵略者（马歇尔，2004）。它们可以立即被激活，并在遇到或遇到病原体时释放许多介质。释放的生物活性分子
直接参与局部炎症反应，但也起作用。
获得性免疫力最佳病原体的起始剂（GALI等，2005；马歇尔，2004）。在我们的研究中，我们观察到金黄色葡萄球菌感染小鼠皮肤，无论是在表皮还是真皮，肥大细胞积累增加。在对照组小鼠中，在同一部位检测到肥大细胞数较少，表明肥大细胞被激活。
金黄色葡萄球菌感染的病程。Tryptase，被激活释放的调解人
肥大细胞定量，结果显示显著增加。
在金黄色葡萄球菌感染小鼠的表皮和真皮中广泛分布，而对照组则几乎不表达。此外，我们从显微镜观察中收集的数据表明，这些活化的肥大细胞可能在
金黄色葡萄球菌诱导的炎症过程。这种相关性包括
先前的研究证明肥大细胞的重要性
登革热病毒感染（King等人，2000）。结果表明肥大细胞和类胰蛋白酶有不同的阶段。
皮肤脓肿是否仍有其他介质尚不清楚。
肥大细胞有助于这种疾病
In a word, our results revealed the underlying involvement of mast
cells and its mediators in the skin abscess behind S. aureus infection.
Moreover, this study provides novel findings that may benefit further
research into skin disorders. Further detailed characterization of the
complex interactions between S. aureus and mast cells will help our
understanding to the pathology of several skins inflammatory diseases.总之，我们的研究结果揭示了桅杆的潜在参与。
金黄色葡萄球菌感染后皮肤脓肿中的细胞及其介质。
此外，这项研究提供了新的发现，可以进一步受益。
皮肤疾病的研究进一步详细描述
金黄色葡萄球菌与肥大细胞之间的复杂相互作用将有助于我们
对几种皮肤炎症性疾病的病理学认识。
Conflict of interest利益冲突
None of the authors has any potential financial conflict of interest
related to this manuscript.
The care and use of experimental animals complied with local animal welfare laws, guidelines and policies.作者没有任何潜在的利益冲突。
与这份手稿有关。
实验动物的照料和使用符合当地动物福利法、指导方针和政策。
Acknowledgments致谢
This work was supported by the National Science Foundation of
China (Grant Nos. 31572485 and 31772709 to D.W), the new faculty
startup research fund of China Three Gorges University (Grant
No·KJ2014B023 to D.W). We thank Dr. Min Li for providing the ST-239
MRSA strain (Shanghai Renji Hospital) in this work.这项工作得到了国家科学基金会的支持。
中国（授予31572485和31772709至DW），新教师
三峡大学仁和医院创业研究基金（补助金）NO·KJ2014B023至D.W）。我们感谢李敏博士提供的ST-23
MRSA株（上海仁济医院）在这项工作中。
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