Lewis R E, Miller R A, Granger H J
Department of Medical Physiology, Texas A & M University, College Station 77843.
Microvasc Res. 1989 Jan;37(1):53-69. doi: 10.1016/0026-2862(89)90072-1.
Acute effects of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) on microvessels of the hamster cheek pouch were studied using intravital and electron microscopy. FMLP (1.0 microM) applied topically to the pouch microvasculature produced transient vasoconstriction of second- and third-order arterioles, which was accompanied by modest narrowing of pericytic venules, leukocyte adherence, diapedesis, and macromolecular extravasation. Contrary to observations of leukotriene B4 (LTB4)-exposed venules in the same animal model, electron micrographs of fMLP-treated venules supported junctional, vesicular, and potential transcellular modes of transendothelial protein transport. Endothelial junctions were not characterized by large gaps, but failure of endothelial processes to effectively bridge diapedesing cells and reestablish junctional contact resulted in substantial deposition of subendothelial reaction product. Venous microvessels 18-21 micron in diameter were particularly susceptible to the deleterious effects of fMLP and revealed the highest percentage of total junctions or endothelial cells labeled by reaction product. Implied barrier dysfunction was more prevalent in fMLP-treated vessels exhibiting adherence and/or diapedesis; however, the presence of barrier defects was not correlated with leukocyte margination and/or emigration (Marg/Emig). The absence of simple correlation, without persuasive evidence for direct vasopermeability effects, recognizes that some Marg/Emig events may not have been present at the time of fixation and suggests the potential for neutrophil-mediated endothelial dysfunction, governed by multiple determinants, is often unrealized.
利用活体显微镜和电子显微镜研究了趋化肽N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）对仓鼠颊囊微血管的急性影响。将fMLP（1.0微摩尔）局部应用于颊囊微血管，可引起二级和三级小动脉短暂性血管收缩，同时伴有周细胞小静脉适度变窄、白细胞黏附、渗出以及大分子物质外渗。与在同一动物模型中观察到的白三烯B4（LTB4）作用下的小静脉不同，fMLP处理后的小静脉电子显微镜图像显示存在跨内皮蛋白转运的连接、囊泡和潜在的跨细胞模式。内皮连接没有明显的大间隙，但内皮细胞突起未能有效桥接渗出细胞并重新建立连接接触，导致内皮下反应产物大量沉积。直径为18 - 21微米的静脉微血管对fMLP的有害影响特别敏感，且被反应产物标记的总连接或内皮细胞百分比最高。在表现出黏附及/或渗出的fMLP处理血管中，隐含的屏障功能障碍更为普遍；然而，屏障缺陷的存在与白细胞靠边及/或移出（Marg/Emig）并无关联。缺乏简单的相关性，且没有直接血管通透性影响的确凿证据，这表明某些Marg/Emig事件在固定时可能并不存在，并提示由多种决定因素控制的中性粒细胞介导的内皮功能障碍潜力往往未得到体现。
