Regulation of the adhesion versus cytotoxic functions of the Mac-1/CR3/alphaMbeta2-integrin glycoprotein.
Regulation of the adhesion versus cytotoxic functions of the Mac-1/CR3/alphaMbeta2-integrin glycoprotein.
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DOI：
10.1615/critrevimmunol.v20.i3.20
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发表时间：
2000
影响因子：
1.3
通讯作者：
Gordon D. Ross
中科院分区：
文献类型：
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作者：
Gordon D. Ross
Mac-1/CR3作为介导白细胞穿过内皮细胞的粘附分子和负责对微生物进行吞噬/脱粒反应的补体iC3b片段的受体。Mac-1/CR3具有许多与其他整合素共享的功能特征，包括通过起源于细胞质域或细胞外区域的构象变化进行双向信号传导。其功能的另一个关键是其与糖基磷脂酰肌醇（GPI）锚固受体（如Fc gammaRIIIB （CD16b）或uPAR (CD87)）形成膜复合物的能力，为这些外膜结合受体提供跨膜信号机制，使其能够介导细胞骨架依赖性粘附或吞噬和脱粒。许多功能似乎依赖于负责识别微生物表面多糖或gpi相关信号伙伴的膜-近端凝集素位点。由于Mac-1/CR3在促进中性粒细胞炎症反应中的重要性，拮抗其功能的治疗策略在治疗自身免疫性疾病和缺血/再灌注损伤方面都显示出希望。相反，与凝集素位点结合的可溶性β -葡聚糖多糖启动循环吞噬细胞和自然杀伤（NK）细胞的Mac-1/CR3，允许细胞毒性脱粒，以响应iC3b-opsonized的肿瘤细胞，否则会逃避这种细胞介导的细胞毒性机制。
Mac-1/CR3 functions as both an adhesion molecule mediating the diapedesis of leukocytes across the endothelium and a receptor for the iC3b fragment of complement responsible for phagocytic/degranulation responses to microorganisms. Mac-1/CR3 has many functional characteristics shared with other integrins, including bidirectional signaling via conformational changes that originate in either the cytoplasmic domain or extracellular region. Another key to its functions is its ability to form membrane complexes with glycosylphosphatidylinositol (GPI)-anchored receptors such as Fc gammaRIIIB (CD16b) or uPAR (CD87), providing a transmembrane signaling mechanism for these outer membrane bound receptors that allows them to mediate cytoskeleton-dependent adhesion or phagocytosis and degranulation. Many functions appear to depend upon a membrane-proximal lectin site responsible for recognition of either microbial surface polysaccharides or GPI-linked signaling partners. Because of the importance of Mac-1/CR3 in promoting neutrophil inflammatory responses, therapeutic strategies to antagonize its functions have shown promise in treating both autoimmune diseases and ischemia/reperfusion injury. Conversely, soluble beta-glucan polysaccharides that bind to its lectin site prime the Mac-1/CR3 of circulating phagocytes and natural killer (NK) cells, permitting cytotoxic degranulation in response to iC3b-opsonized tumor cells that otherwise escape from this mechanism of cell-mediated cytotoxicity.