Monocyte chemoattractants in pigeon aortic atherosclerosis

Abstract

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.