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

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.

Review of Cerebral Aneurysm Formation, Growth, and Rupture

“…7 Interestingly, macrophages seem to be present in human CAs in 2 different forms that exert opposite effects on inflammation. 8 Whereas the proinflammatory M1 cells and the anti-inflammatory M2 cells are present in equal proportion in unruptured aneurysms, the balance shifts toward M1 cells in ruptured aneurysms, suggesting a role for M1/M2 imbalance in the progression of human CAs to rupture. 8 Also, the critical role of macrophages in CAs has allowed the development of targeted molecular imaging for identifying rupture-prone aneurysms, 9,10 and this will be discussed in further detail below.…”

“…8 Whereas the proinflammatory M1 cells and the anti-inflammatory M2 cells are present in equal proportion in unruptured aneurysms, the balance shifts toward M1 cells in ruptured aneurysms, suggesting a role for M1/M2 imbalance in the progression of human CAs to rupture. 8 Also, the critical role of macrophages in CAs has allowed the development of targeted molecular imaging for identifying rupture-prone aneurysms, 9,10 and this will be discussed in further detail below. Therapies targeting macrophage activation and MMP release in aneurysm walls or preventing the M1/M2 imbalance may potentially halt aneurysm formation and rupture.…”

Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

“…[19] Further connection has been found between macrophage presence and aneurysm rupture. Hasan et al [22] showed that in human cerebral aneurysms, M1 and M2 macrophages were found to be in equal proportions; however, M1 macrophages presented in higher levels than M2 macrophages in ruptured human cerebral aneurysms. This means that there were more macrophages promoting inflammation, M1 macrophages, than macrophages working to repair the vessel tissue and decrease inflammation, M2 macrophages.…”

“…This imbalance was also correlated with an increase in mast cell presence in ruptured aneurysms. [22] The role of the inflammatory mediators, chemokines, has been studied in aneurysm formation. Chemokines promote chemotaxis in particular, the migration of inflammatory cells during the inflammatory response.…”

Equivocal usefulness of FDG for the noninvasive imaging of abdominal aortic aneurysms

“…2. As observed in atherosclerotic lesions in which M1/M2 macrophage polarization occurs resulting in the presence of a continuum of proatherogenic and antiatherogenic cells in atherosclerotic plaques [12], an imbalance in M1/M2 macrophages has been observed in ruptured vs. unruptured human cerebral aneurysms [13]. Should these findings be replicated in AAA, FDG imaging would not be likely to allow the differentiation between proinflammatory (M1) and antiinflammatory (M2) macrophages, thereby reducing its relevance for the identification of prone-torupture aneurysms.…”