neutrophil infiltration and oxidant production in human atherosclerotic carotid plaques

• DOI: 10.14670/hh-26.1
• Publication Date: 2011-01-01
• Authors: Hosokawa, Takatoshi; Kumon, Yoshitaka; Kobayashi, Toshihiro; Enzan, Hideaki; Nishioka, Yutaka; Yuri, Kazunari; Wakiguchi, Hiroshi; Sugiura, Tetsuro
• Keywords: Aged, 80 and over; Inflammation; Male; Naphthol AS D Esterase; Neutrophils; Macrophages; Antigens, Differentiation, Myelomonocytic; NADPH Oxidases; Middle Aged; Atherosclerosis; GPI-Linked Proteins; Oxidants; Immunohistochemistry; Neutrophil Infiltration; Antigens, CD; Humans; Carotid Stenosis; Female; Cell Adhesion Molecules; 61 - Medicina; Aged

To clarify the clinical implications of neutrophils in vulnerable plaques we evaluated the function and activity of infiltrated neutrophils in an atherosclerotic plaque, focusing on oxidant production. A histopathological investigation was performed using carotid arterial samples obtained from seven patients. The atherosclerotic plaques were examined cytochemically for naphthol-ASD-chloroacetate esterase activity and oxidant-production, and immunohistochemically using N-formyl peptide receptor-like 1 (fPRL1)-, CD66b-, CD68- or p22phox-specific antibodies. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque was estimated using an activity index. Naphthol-ASD-chloroacetate esterase activity was found in cells located in the atherosclerotic plaque, indicating that the cells were neutrophils. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque decreased to approximately 60% of the intensity observed in the capillary vessels. Oxidant-production was also detected in the plaques, and both neutrophils and macrophages were observed at the corresponding oxidant-production sites. p22phox expression was also located in the same areas in which oxidant-production was observed in these plaques. We could not directly evaluate how much ROS generated from the infiltrated neutrophils contributed the plaque vulnerability followed by its rupture. However, the infiltrated neutrophils in the atherosclerotic plaques morphologically appeared activated and were actively generating oxidant, implying that neutrophils, together with macrophages, infiltrate into atherosclerotic plaques and contribute to plaque vulnerability.