Witkowska Danuta, Bartyś Arkadiusz, Gamian Andrzej
Laboratorium Mikrobiologii Lekarskiej Instytutu Immunologii i Terapii Doświadczalnej PAN im. L.Hirszfelda we Wrocławiu.
Postepy Hig Med Dosw (Online). 2008 Dec 22;62:694-707.
Defensins and cathelicidins belong to antimicrobial peptides (AMP), called also the natural antibiotics. They are found in Prokaryotes and Eukaryotes, also are synthesized in plants. These molecules were described in bacteria, invertebrates, vertebrates, also in mammals including humans. The amino-acids sequence is determined for about 880 antimicrobial peptides, and their classification is difficult and complex. These oligo- and polypeptides, are killing the microbes or inhibit their growth, are bactericidal to Gram-negative, Gram-positive bacteria, neutralizing toxins, demonstrated antiviral activity. AMP are multifunctional molecules, playing the first line of defense in human organism as effectors of unspecific immunity, with a broad spectrum of activity against pathogens, are characterized by controlling the physiological bacterial flora, often acting synergistically, are produced in different cells as defense against mechanisms of microbial resistance. They are chemotactic to neutrophiles and T cells, activate the dendritic cells. In human organism defensins are expressed in several cells and tissues, in neutrophiles, platelets, epithelial cells, in liver, skin, eye conjunctiva. Deficiency of defensins or cathelicidins cause pathological symptoms in atopic allergies or in Kostman disease. Several synthetic peptides are currently at the final phases of clinical trials regarding treatment of various bacterial infections. Defensins or cathelicidins could be also efficient as adjuvants or carriers for vaccines, in dairy industry as preservatives. This work presents some problems concerning the occurrence of AMP, especially defensins and cathelicidins of mammals, their classification, structure, various functions and mechanisms of bactericidal activity, and also their use in treatment of some infectious diseases.
防御素和cathelicidin属于抗菌肽(AMP),也被称为天然抗生素。它们存在于原核生物和真核生物中,也在植物中合成。这些分子在细菌、无脊椎动物、脊椎动物以及包括人类在内的哺乳动物中都有描述。已确定约880种抗菌肽的氨基酸序列,其分类困难且复杂。这些寡肽和多肽可杀死微生物或抑制其生长,对革兰氏阴性菌、革兰氏阳性菌具有杀菌作用,能中和毒素,还具有抗病毒活性。抗菌肽是多功能分子,作为非特异性免疫的效应器在人体中发挥第一道防线的作用,对病原体具有广泛的活性,其特点是控制生理性细菌菌群,常协同发挥作用,在不同细胞中产生以抵御微生物耐药机制。它们对嗜中性粒细胞和T细胞具有趋化作用,可激活树突状细胞。在人体中,防御素在多种细胞和组织中表达,如嗜中性粒细胞、血小板、上皮细胞、肝脏、皮肤、眼结膜。防御素或cathelicidin的缺乏会在特应性过敏或科斯特曼病中引发病理症状。目前有几种合成肽正处于治疗各种细菌感染的临床试验最后阶段。防御素或cathelicidin还可作为疫苗的佐剂或载体发挥作用,在乳制品行业用作防腐剂。本文介绍了一些关于抗菌肽,尤其是哺乳动物防御素和cathelicidin的存在、分类、结构、各种功能和杀菌活性机制以及它们在治疗某些传染病中的应用等问题。