MAST細胞について
MAST細胞(マスト細胞)は、主にアレルギー反応に関与する細胞の一種です。正式には、マスト細胞とは、マスト細胞膜タンパク質(MAST)を発現する細胞を指します。このタンパク質は、アレルギー反応において重要な役割を果たしています。
MAST細胞は、アレルギー症状を引き起こす主要な細胞の一つであり、アレルギー症状の発現や重症度に関与しています。MAST細胞の活動を抑えることで、アレルギー症状を軽減する治療法が研究されています。
気管支、鼻粘膜、皮膚など外界と接触する組織の粘膜や結合組織に存在する、造血幹細胞由来の細胞。炎症や免疫反応などの生体防御機構に重要な役割を持ち、IgEを介したI型アレルギー反応の主要な役割を演じる。細胞表面にIgE特異的受容体を介しIgE抗体を保持することができ、IgEに抗原(アレルゲン)が結合すると、IgE受容体が架橋されることで脱顆粒反応を起こし、顆粒内容物のヒスタミンなどを放出する。また、細胞膜酵素の活性化により、アラキドン酸の生成と代謝を亢進させ、ロイコトリエン、血小板活性化因子(PAF)、プロスタグランジン類、トロンボキサンA2などを遊離する。こうして肥満細胞から遊離されたケミカルメディエーターに気管支平滑筋収縮作用、血管透過性亢進作用、粘液分泌作用などがあり、I型アレルギーにおける即時型反応を引き起こす。なお肥満細胞という名称であるが、肥満症とは無関係である。
Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes.
Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators.
These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.
mast 細胞の単離は難しい
The unraveling of mast cell functions, in addition to their established and extensively studied role in IgE-mediated reactions, has been the focus of mast cell research in the past decades. Nevertheless, the identification of mast cell functions has progressed slowly due to difficulties in accessing these cells in vivo and the obstacles encountered when obtaining them both by enzymatic dispersion of tissues or by culture of mast cell progenitors isolated from the bone marrow, peripheral or umbilical cord blood. The culture of mast cell progenitors yields a small number of mast cells and is often expensive and time consuming, and results in variable phenotypes as a consequence of culture conditions (Moon et al. 2010).
The use of mast cell lines has greatly facilitated the characterization of various aspects of mast cell function. However, as transformed cells, they present limitations and the results obtained through their use must be interpreted cautiously when extrapolating to mast cell functions in vivo. Mouse strains that are deficient in mast cells due to mutations in the Kit or Stem Cell Factor (SCF) gene (KitW/W-v, KitW-sh, and Sl/Sld) have served as valuable tools for defining and inferring mast cell functions in vivo (Kitamura et al. 1978; Russell 1979; Grimbaldeston et al. 2005). However, these mice bear several other abnormalities resulting from Kit’s role in other cells, which include erythrocytes, neutrophils and melanocytes, as well as other cell lineages. The engraftment of bone marrow or bone marrow-derived mast cells (BMMCs) in these deficient strains has helped to shed light on mast cell origin and to reliably establish connections between mast cell functions in vivo and their involvement in several diseases (Kitamura et al. 1977; Kitamura et al. 1978; Grimbaldeston et al. 2005; Galli and Tsai 2008; Jamur and Oliver 2011).