Denholm E M, Lewis J C
Am J Pathol. 1987 Mar;126(3):464-75.
Atherosclerosis occurs in the aorta of White Carneau pigeons proximal to the celiac bifurcation, where monocyte adhesion and migration into lesions have been demonstrated. This study documents chemoattractants that might be responsible for monocyte adherence and migration. Ten-week-old pigeons were fed either a cholesterol-free (normal) diet or a 0.4% cholesterol diet for 12 or 24 weeks. Birds with a normal diet did not have lesions in the lesion-prone area of the aorta, whereas birds fed a cholesterol-containing diet had simple intimal foam-cell lesions (12 weeks) or foam-cell lesions complicated with extracellular lipid and fibrillar matrix material (24 weeks). Plasma cholesterol levels in birds on the cholesterol-containing diet were 780-1080 mg/dl versus 140-240 mg/dl in the normal diet control group(s) at necropsy. To assay for chemoattractants, tissue was collected from lesion-prone and nonsusceptible (nonlesion) areas of the aortas. Samples from the two types of regions were separately pooled, then homogenized and tested for chemoattractant activity for pigeon peripheral blood monocytes. Monocyte chemoattractants were demonstrated in lesion area homogenates from pigeons fed cholesterol for 12 or 24 weeks and also in analogous homogenates from pigeons fed a normal diet. Monocyte migration to lesion-prone homogenates was significantly greater than that to nonlesion area homogenates. The chemoattractants in homogenates were monocyte-specific. The chemoattractant activity in the birds fed cholesterol for 12 weeks was confined to the aqueous phase of lipid extracts. This activity was abolished by pronase but unaffected by heat (100 C, 30 minutes), which indicated that the chemoattractant(s) in these homogenates was heat-stable protein(s). Activity in lipid extracts of lesion area homogenates from birds fed a cholesterol-containing diet for 24 weeks was found in both the aqueous and organic phases, suggesting that these samples contained lipid as well as proteinaceous chemoattractants.
动脉粥样硬化发生在白卡诺鸽主动脉腹腔干分叉近端,在此处已证实有单核细胞黏附并迁移至病变部位。本研究记录了可能导致单核细胞黏附和迁移的趋化因子。将10周龄的鸽子分别喂食不含胆固醇(正常)的饮食或含0.4%胆固醇的饮食,持续12周或24周。正常饮食的鸽子在主动脉易病变区域没有病变,而喂食含胆固醇饮食的鸽子有单纯内膜泡沫细胞病变(12周)或伴有细胞外脂质和纤维状基质材料的泡沫细胞病变(24周)。尸检时,喂食含胆固醇饮食的鸽子血浆胆固醇水平为780 - 1080 mg/dl,而正常饮食对照组为140 - 240 mg/dl。为检测趋化因子,从主动脉的易病变和不易感(无病变)区域收集组织。将两种区域的样本分别汇集,然后匀浆,并检测对鸽外周血单核细胞的趋化活性。在喂食胆固醇12周或24周的鸽子的病变区域匀浆中以及喂食正常饮食的鸽子的类似匀浆中均证实有单核细胞趋化因子。单核细胞向易病变匀浆的迁移显著大于向无病变区域匀浆的迁移。匀浆中的趋化因子对单核细胞具有特异性。喂食胆固醇12周的鸽子匀浆中的趋化活性局限于脂质提取物的水相。该活性被链霉蛋白酶消除,但不受热(100℃,30分钟)影响,这表明这些匀浆中的趋化因子是热稳定蛋白。在喂食含胆固醇饮食24周的鸽子的病变区域匀浆的脂质提取物中,水相和有机相中均发现有活性,这表明这些样本中既含有脂质趋化因子也含有蛋白质趋化因子。