Lipopolysaccharides (LPSs or endotoxins) from Gram-negative bacteria represent pathogen-associated molecular patterns (PAMPs) that are recognized by CD14 and Toll-like receptor 4 (TLR4). Lipopolysaccharides prime polymorphonuclear leukocytes (PMNs) for substantial production of reactive oxygen species (ROS) during its response to secondary stimuli such as chemoattractants or pathogens. The excessive ROS production can damage surrounding host tissues, thereby amplifying the inflammatory reaction caused by pathogens. Today, specific antibodies against CD14, TLR4, and CD11b are being used as the essential tools to elucidate the role of these receptors in acute inflammation and some of these antibodies have advised as therapeutic agents for clinical use. Because each antibody has two antigen-binding arms [F(ab)₂] and one Fc arm, its effect on cellular response is much more complicated rather than simple blockage of target receptor. In fact, IgG antibody, once bound to target receptor, engages Fc receptors γ (FcγRs) and thereby is able to activate the adaptive immune system. The consequences of antibody-dependent binary heterotypic association of CD14, TLR4, or CD11b with FcγRs as well as homotypic one on ROS production are not well elucidated. Moreover, the consequences of antigenic recognition of CD14, TLR4, or CD11b by specific F(ab)₂ fragments are not always investigated. In this review, we will discuss known mechanisms underlying the therapeutic efficiency of CD14, TLR4, and CD11b/CD18 antibodies with a focus on LPS-dependent ROS or cytokine production by PMNs or monocytes. The impacts of F(ab)₂ as well as antibody IgG subclasses (isotypes) in therapeutic efficiency or agonistic potency of known antibodies against abovementioned receptors are presented. We also pay attention to how the efficiency of different IgG antibody subclasses is modulated during LPS-induced inflammation and by production of priming agents such as interferon γ (IFN-γ). Our review reinforces the molecular targets and therapeutic approaches to amelioration of harmful consequences of excessive activation of human pattern recognition receptors.

中文翻译：

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CD14，TLR4或CD11b单克隆抗体：表位和同种型特异性对人粒细胞和单核细胞产生ROS的影响

来自革兰氏阴性细菌的脂多糖（LPS或内毒素）代表被CD14和Toll样受体4（TLR4）识别的病原体相关分子模式（PAMP）。脂多糖可引发多形核白细胞（PMN），在其对诸如化学引诱剂或病原体等次级刺激的反应过程中大量产生活性氧（ROS）。过量的ROS产生会损坏周围的宿主组织，从而放大由病原体引起的炎症反应。如今，针对CD14，TLR4和CD11b的特异性抗体被用作阐明这些受体在急性炎症中的作用的重要工具，并且其中一些抗体已被建议用作临床治疗剂。因为每种抗体都有两个抗原结合臂[F（ab ）₂）和一个Fc臂，其对细胞反应的作用要比对目标受体的简单阻断要复杂得多。事实上，IgG抗体，一旦结合到靶受体，接合Fc受体γ（FC γ RS），从而能够激活适应性免疫系统。CD14，TLR4，或细胞CD11b的抗体依赖的二进制异型伴随Fc的后果γ卢比以及对ROS产生的同型一个没有得到很好的阐述。此外，特异性F（ab ）₂抗原识别CD14，TLR4或CD11b的后果碎片并不总是被调查。在这篇综述中，我们将讨论CD14，TLR4和CD11b / CD18抗体的治疗效率基础的已知机制，重点是PMN或单核细胞对LPS依赖性ROS或细胞因子的产生。提出了F（ab ）₂以及抗体IgG亚类（同种型）对已知抗体针对上述受体的治疗效率或激动作用的影响。我们还注意在LPS诱导的炎症过程中，如何通过产生诸如干扰素γ（IFN- γ）的引发剂来调节不同IgG抗体亚类的效率）。我们的综述加强了分子靶标和治疗方法，以改善人类模式识别受体过度激活的有害后果。