Travers J B, Harrison K A, Johnson C A, Clay K L, Morelli J G
Department of Dermatology, University of Colorado Health Sciences Center, Denver, USA.
J Invest Dermatol. 1996 Jul;107(1):88-94. doi: 10.1111/1523-1747.ep12298295.
Platelet-activating factor (PAF) is a potent inflammatory mediator that is thought to play a role in cutaneous inflammation. These studies used mass spectrometry to examine the molecular species of PAF precursor glycerophosphocholine lipids (GPC) as well as the biosynthesis of PAF and other sn-2 acetyl-GPC in a human keratinocyte-derived cell line (HaCaT keratinocytes). Approximately 28% of HaCaT keratinocyte GPC consisted of 1-alkyl species, and the relative amounts of the sn-1 alkyl constituents of the PAF precursor 1-alkyl-2-acyl-GPC were as follows: hexadecyl > octadecenyl > octadecyl. Ionophore (A23187)-stimulated HaCaT keratinocytes synthesized both PAF (1-hexadecyl, 1-octadecenyl, and 1-octadecyl species) and less potent 1-acyl analogs (1-palmitoyl, 1-oleoyl, and 1-stearoyl species). PAF production was rapid and maximal by 10 min. The major species of sn-2acetyl-GPC at 2.5 min were 1-hexadecyl-2-acetyl-GPC (2.2 ng/10(6) cells) and 1-palmitoyl-2-acetyl-GPC (2.4 ng/10(6) cells). HaCaT keratinocytes also synthesized PAF and 1-acyl PAF analogs when stimulated with the peptide growth factor endothelin-1 and the nonhydrolyzable PAF receptor agonist carbamyl-PAF. Both 1-hexadecyl-2- acetyl-GPC and 1-palmitoyl-2-acetyl-GPC stimulated intracellular calcium mobilization in HaCaT cells, indicating that these sn-2 acetyl-GPC act in autocrine fashion. These studies revealed that the human keratinocyte-derived cell line HaCaT can synthesize significant amounts of PAF and 1-acyl analogs in vitro from both nonspecific (A23187) and specific (endothelin-1, carbamyl-PAF) stimulation, suggesting a role for this inflammatory lipid mediator in keratinocyte pathophysiology.
血小板活化因子（PAF）是一种强效的炎症介质，被认为在皮肤炎症中起作用。这些研究使用质谱法检测了PAF前体甘油磷酸胆碱脂质（GPC）的分子种类，以及人角质形成细胞系（HaCaT角质形成细胞）中PAF和其他sn-2乙酰基-GPC的生物合成。约28%的HaCaT角质形成细胞GPC由1-烷基种类组成，PAF前体1-烷基-2-酰基-GPC的sn-1烷基成分的相对含量如下：十六烷基>十八碳烯基>十八烷基。离子载体（A23187）刺激的HaCaT角质形成细胞合成了PAF（1-十六烷基、1-十八碳烯基和1-十八烷基种类）以及活性较低的1-酰基类似物（1-棕榈酰基、1-油酰基和1-硬脂酰基种类）。PAF的产生迅速，在10分钟时达到最大值。在2.5分钟时，sn-2乙酰基-GPC的主要种类是1-十六烷基-2-乙酰基-GPC（2.2 ng/10⁶细胞）和1-棕榈酰基-2-乙酰基-GPC（2.4 ng/10⁶细胞）。当用肽生长因子内皮素-1和不可水解的PAF受体激动剂氨甲酰-PAF刺激时，HaCaT角质形成细胞也合成PAF和1-酰基PAF类似物。1-十六烷基-2-乙酰基-GPC和1-棕榈酰基-2-乙酰基-GPC均刺激HaCaT细胞内的钙动员，表明这些sn-2乙酰基-GPC以自分泌方式起作用。这些研究表明，人角质形成细胞系HaCaT在体外可通过非特异性（A23187）和特异性（内皮素-1、氨甲酰-PAF）刺激合成大量的PAF和1-酰基类似物，提示这种炎症脂质介质在角质形成细胞病理生理学中发挥作用。
