van Wetering S, Sterk P J, Rabe K F, Hiemstra P S
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
J Allergy Clin Immunol. 1999 Dec;104(6):1131-8. doi: 10.1016/s0091-6749(99)70004-7.
Antimicrobial peptides have been identified as key elements in the innate host defense against infection. Recent studies have indicated that the activity of antimicrobial peptides may be decreased in cystic fibrosis, suggesting a major role for these peptides in host defense against infection. One of the most intensively studied classes of antimicrobial peptides are defensins. Defensins comprise a family of cationic peptides that in human subjects can be divided into the alpha- and beta-defensin subfamilies. The alpha-defensins are produced by neutrophils and intestinal Paneth's cells, whereas beta-defensins are mainly produced by epithelial cells. Although studies on beta-defensins have so far focused on their antimicrobial activity, studies on alpha-defensins have suggested a role of these peptides in inflammation, wound repair, and specific immune responses. alpha-Defensins, which accumulate in airway secretions of patients with various chronic inflammatory lung disorders, were shown to be cytotoxic toward airway epithelial cells and to induce chemokine secretion in several cell types. Furthermore, the capacity of alpha-defensins to promote bacterial adherence to epithelial cells in vitro further supports a role for these peptides in the pathogenesis of chronic obstructive pulmonary disease and cystic fibrosis. Increased numbers of neutrophils are also present in the airways of patients with asthma, suggesting that neutrophils are involved in the pathogenesis of this disease. Because defensins are able to induce histamine release by mast cells and increase the airway hyperresponsiveness to histamine, it is tempting to speculate that defensins may also contribute to the inflammatory processes in asthma. Besides these proinflammatory effects, alpha-defensins may also display anti-inflammatory activities, including regulation of complement activation and proteinase inhibitor secretion. Finally, defensins may be involved in wound repair because defensins increase epithelial cell proliferation. Thus recent defensin research has revealed potential links between the innate and acquired immune system.
抗菌肽已被确认为宿主抵御感染的固有防御中的关键要素。最近的研究表明，在囊性纤维化患者中抗菌肽的活性可能会降低，这表明这些肽在宿主抵御感染中起主要作用。研究最为深入的一类抗菌肽是防御素。防御素是一类阳离子肽家族，在人类中可分为α-防御素和β-防御素亚家族。α-防御素由中性粒细胞和肠道潘氏细胞产生，而β-防御素主要由上皮细胞产生。尽管迄今为止对β-防御素的研究主要集中在其抗菌活性上，但对α-防御素的研究表明这些肽在炎症、伤口修复和特异性免疫反应中发挥作用。在患有各种慢性炎症性肺部疾病的患者气道分泌物中积累的α-防御素，对气道上皮细胞具有细胞毒性，并能在几种细胞类型中诱导趋化因子分泌。此外，α-防御素在体外促进细菌黏附于上皮细胞的能力进一步支持了这些肽在慢性阻塞性肺疾病和囊性纤维化发病机制中的作用。哮喘患者气道中也存在数量增加的中性粒细胞，这表明中性粒细胞参与了该疾病的发病机制。由于防御素能够诱导肥大细胞释放组胺并增加气道对组胺的高反应性，因此很容易推测防御素也可能参与哮喘的炎症过程。除了这些促炎作用外，α-防御素还可能表现出抗炎活性，包括调节补体激活和蛋白酶抑制剂分泌。最后，防御素可能参与伤口修复，因为防御素可增加上皮细胞增殖。因此，最近对防御素的研究揭示了固有免疫系统和获得性免疫系统之间的潜在联系。
