Role of proinflammatory CD68+ mannose receptor-macrophages in peroxiredoxin-1 expression and in abdominal aortic aneurysms in humans

Abstract

Objective-: Abdominal aortic aneurysms (AAAs), dilations of the infrarenal aorta, are characterized by inflammation and oxidative stress. We previously showed increased levels of peroxiredoxin-1 (PRDX-1) in macrophages cultured from AAA patients. The purpose of the study was to determine which subpopulation of macrophages is present in AAAs and is involved in upregulation of PRDX-1 in aneurysmal disease. METHODS AND RESULTS-: This study used immunohistochemistry with antibodies against CD68 and mannose receptor (MR) to determine the subtype of macrophages in AAA tissue samples (n=33); laser capture microdissection to isolate each subtype; and quantitative-reverse transcriptase-polymerase chain reaction, Western blot, and ELISA to assess PRDX-1 mRNA and PRDX-1protein levels in both types. Proinflammatory CD68MR macrophages predominated in adventitial tissue, whereas the intraluminal thrombus contained CD68MR macrophages. The presence of lipids and iron-containing deposits confirmed their phagocytic phenotype. Laser capture microdissection-isolated CD68MR and CD68MR macrophages, characterized by quantitative-reverse transcriptase-polymerase chain reaction (TNF, IL1B, MRC1, and CCL18) and Western blot (stabilin and hemoglobin), validated the microdissected subtypes. PRDX-1 expression was colocalized with CD68MR macrophages. PRDX-1 mRNA and PRDX-1 protein were both more abundant in CD68MR than CD68MR macrophages in AAA. CONCLUSION-: These findings suggest that the proteins or mRNAs expressed by the proinflammatory CD68MR macrophages may contribute to aneurysmal pathology. © 2012 American Heart Association, Inc.