Role of Proinflammatory CD68⁺MR⁻ Macrophages in Peroxiredoxin-1 Expression and in Abdominal Aortic Aneurysms in Humans

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 CD68⁺MR⁻ macrophages predominated in adventitial tissue, whereas the intraluminal thrombus contained CD68⁺MR⁺ macrophages. The presence of lipids and iron-containing deposits confirmed their phagocytic phenotype. Laser capture microdissection-isolated CD68⁺MR⁻ and CD68⁺MR⁺ 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 CD68⁺MR⁻ macrophages. PRDX-1 mRNA and PRDX-1 protein were both more abundant in CD68⁺MR⁻ than CD68⁺MR⁺ macrophages in AAA.

Conclusion—These findings suggest that the proteins or mRNAs expressed by the proinflammatory CD68⁺MR⁻ macrophages may contribute to aneurysmal pathology.