Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: preliminary results

David Hasan,Nohra Chalouhi,Tomoki Hashimoto,Pascal Jabbour

doi:10.1186/1742-2094-9-222

Abstract

BackgroundM1 and M2 cells are two major subsets of human macrophages that exert opposite effects on the inflammatory response. This study aims to investigate the role of macrophage M1/M2 imbalance and mast cells in the progression of human cerebral aneurysms to rupture.MethodsTen patients with cerebral aneurysms (five ruptured and five unruptured) underwent microsurgical clipping. During the procedure, a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for M1 cells (anti-HLA DR), M2 cells (anti-CD 163), and mast cells (anti-tryptase clone AA). A segment of the superficial temporal artery (STA) was also removed and immunostained with monoclonal antibodies for M1, M2, and mast cells.ResultsAll ten aneurysm tissues stained positive for M1, M2, and mast cells. M1 and M2 cells were present in equal proportions in unruptured aneurysms. This contrasted with a marked predominance of M1 over M2 cells in ruptured aneurysms (p = 0.045). Mast cells were also prominently upregulated in ruptured aneurysms (p = 0.001). Few M1 and M2 cells were present in STA samples.ConclusionsM1/M2 macrophages and mast cells are found in human cerebral aneurysms; however, M1 and mast cell expression seems to markedly increase in ruptured aneurysms. These findings suggest that macrophage M1/M2 imbalance and upregulation of mast cells may have a role in the progression of cerebral aneurysms to rupture.

Highlights

M1 and M2 cells are two major subsets of human macrophages that exert opposite effects on the inflammatory response
Two major subsets of human macrophages can be defined in atherosclerotic plaques: CD14highCD16low macrophages, which typically represent 85% to 95% of monocytes, and CD14lowCD16high macrophages, which account for the remaining 5 to 15% [2,3,4,7]
All 20 specimens (10 aneurysms and 10 superficial temporal artery (STA)) were immunostained with monoclonal antibodies to mast cells using anti-mast cells tryptase clone AA1 (DakoCytomation, Carpentaria, CA), M1 cells using anti-HLA DR (ABCAM, Cambridge MA), and M2 cells using anti-CD 163 (ABCAM, Cambridge MA)

Summary

Introduction

M1 and M2 cells are two major subsets of human macrophages that exert opposite effects on the inflammatory response. This study aims to investigate the role of macrophage M1/M2 imbalance and mast cells in the progression of human cerebral aneurysms to rupture. Two major subsets of human macrophages can be defined in atherosclerotic plaques: CD14highCD16low macrophages, which typically represent 85% to 95% of monocytes, and CD14lowCD16high macrophages, which account for the remaining 5 to 15% [2,3,4,7]. Macrophages play a critical role in cerebral aneurysm formation and rupture [10,11,12,13]. Recent studies have revealed that mast cells contribute to various vascular diseases through degranulation and release of cytokines including cerebral aneurysm formation [14,15]

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