Howell Michael D, Jones James F, Kisich Kevin O, Streib Joanne E, Gallo Richard L, Leung Donald Y M
Division of Allergy and Immunology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
J Immunol. 2004 Feb 1;172(3):1763-7. doi: 10.4049/jimmunol.172.3.1763.
Possible bioterrorism with smallpox has led to the resumption of smallpox (vaccinia virus) immunization. One complication, eczema vaccinatum, occurs primarily in patients with atopic dermatitis (AD). Skin lesions of patients with AD, but not psoriasis, is deficient in the cathelicidin antimicrobial peptide (LL-37) and human beta-defensin-2 (HBD-2). We hypothesized that this defect may explain the susceptibility of patients with AD to eczema vaccinatum. The Wyeth vaccine strain of vaccinia virus was incubated with varying concentrations of human (LL-37) and murine (CRAMP) cathelicidins, human alpha-defensin (HBD-1, HBD-2), and a control peptide. Outcomes included quantification of viral PFU, vaccinia viral gene expression by quantitative real-time RT-PCR, and changes in virion structure by transmission electron microscopy. CRAMP knockout mice and control animals were inoculated by skin pricks with 2 x 10(5) PFU of vaccinia and examined daily for pox development. Physiologic amounts of human and murine cathelicidins (10-50 micro M), but not human defensins, which had antibacterial activity, resulted in the in vitro reduction of vaccinia viral plaque formation (p < 0.0001), vaccinia mRNA expression (p < 0.001), and alteration of vaccinia virion structure. In vivo vaccinia pox formation occurred in four of six CRAMP knockout animals and in only one of 15 control mice (p < 0.01). These data support a role for cathelicidins in the inhibition of orthopox virus (vaccinia) replication both in vitro and in vivo. Susceptibility of patients with AD to eczema vaccinatum may be due to a deficiency of cathelicidin.
天花可能被用于生物恐怖主义，这导致了天花（痘苗病毒）免疫接种的恢复。一种并发症，即牛痘性湿疹，主要发生在特应性皮炎（AD）患者中。AD患者而非银屑病患者的皮肤病变中，抗菌肽cathelicidin（LL-37）和人β-防御素-2（HBD-2）缺乏。我们推测这种缺陷可能解释了AD患者对牛痘性湿疹的易感性。将痘苗病毒的惠氏疫苗株与不同浓度的人（LL-37）和鼠（CRAMP）cathelicidin、人α-防御素（HBD-1、HBD-2）以及一种对照肽一起孵育。结果包括病毒空斑形成单位（PFU）的定量、通过定量实时逆转录聚合酶链反应（RT-PCR）检测痘苗病毒基因表达以及通过透射电子显微镜观察病毒粒子结构的变化。通过皮肤针刺给CRAMP基因敲除小鼠和对照动物接种2×10⁵ PFU的痘苗，并每天检查痘疹发展情况。具有抗菌活性的人及鼠cathelicidin的生理量（10 - 50 μM），而非人防御素，导致痘苗病毒空斑形成在体外减少（p < 0.0001）、痘苗病毒mRNA表达减少（p < 0.001）以及痘苗病毒粒子结构改变。在体内，6只CRAMP基因敲除动物中有4只出现了痘苗痘疹，而15只对照小鼠中只有1只出现（p < 0.01）。这些数据支持了cathelicidin在体外和体内抑制正痘病毒（痘苗病毒）复制中的作用。AD患者对牛痘性湿疹的易感性可能是由于cathelicidin缺乏。
