Dermatology Service, Hospital Universitario de Canarias, University of La Laguna, Tenerife, Spain.
J Invest Dermatol. 2011 Nov;131(11):2263-70. doi: 10.1038/jid.2011.210. Epub 2011 Jul 28.
Two critical defensive functions of the outer epidermis, the permeability barrier and antimicrobial defense, share certain structural and biochemical features. Moreover, three antimicrobial peptides (AMPs), i.e., mouse β-defensin 3 (mBD3), mouse cathelicidin antimicrobial peptide (mCAMP), and the neuroendocrine peptide, catestatin (Cst), all localize to the outer epidermis, and both mBD3 and mCAMP are secreted from the epidermal lamellar bodies with other organelle contents that subserve the permeability barrier. These three AMPs are upregulated in response to acute permeability barrier disruption, whereas conversely, mCAMP-/- mice (unable to combat Gram-positive pathogens) also display abnormal barrier homeostasis. To determine further whether these two functions are co-regulated, we investigated changes in immunostaining for these three AMPs in skin samples in which the permeability barrier function in mice had been either compromised or enhanced. Compromised or enhanced barrier function correlated with reduced or enhanced immunohistochemical expression of mCAMP, respectively, but conversely with Cst expression, likely due to the role of this AMP as an endogenous inhibitor of cathelicidin expression. mBD3 expression correlated with experimental barrier perturbations, but poorly with developmental changes in barrier function. These studies show that changes in cathelicidin and Cst expression parallel changes in permeability barrier status, with a less clear relationship with mBD3 expression.
外皮层的两个关键防御功能，即渗透性屏障和抗菌防御，具有某些结构和生化特征。此外，三种抗菌肽（AMPs），即小鼠 β-防御素 3（mBD3）、小鼠抗菌肽 cathelicidin（mCAMP）和神经内分泌肽 catestatin（Cst），均定位于外皮层，mBD3 和 mCAMP 均从表皮板层小体分泌出来，其他细胞器的内容物为渗透性屏障提供服务。这三种 AMPs 在急性渗透性屏障破坏时会被上调，而相反，mCAMP-/- 小鼠（无法对抗革兰氏阳性病原体）也表现出异常的屏障稳态。为了进一步确定这两个功能是否协同调节，我们研究了在小鼠皮肤渗透性屏障功能受损或增强的皮肤样本中，这三种 AMP 的免疫染色变化。分别与 mCAMP 的免疫组织化学表达减少或增强相关，而与 Cst 表达相反，这可能是由于该 AMP 作为 cathelicidin 表达的内源性抑制剂的作用。mBD3 的表达与实验性屏障干扰相关，但与屏障功能的发育变化相关性较差。这些研究表明，cathelicidin 和 Cst 的表达变化与渗透性屏障状态的变化平行，与 mBD3 的表达相关性较差。
