Cigarette Smoke Extract Activates Tartrate-Resistant Acid Phosphatase-Positive Macrophage

Abstract

Background: It has been reported that smoking is one of the strongest positive risk factors for abdominal aortic aneurysms (AAAs). Although many studies have been directed to decipher the effect of smoking on AAA, its effect on macrophage activation has not yet been explored. Objectives:We have reported the importance of osteoclastogenesis (OCG) in aneurysm formation. Therefore, we examined the effect of cigarette smoking on OCG and arterial aneurysmal formation by using cigarette smoke extract (CSE) in this study.Methods: Macrophage cell lines were stimulated with CSE, and their activation and differentiation were examined in vitro. Since macrophages activated through the OCG pathway are identified by tartrate-resistant acid phosphatase (TRAP) expression, these cells are referred to as TRAP-positive macrophages (TPMs) in this study. We also applied CSE-contained PBS in the calcium chloride-induced mouse carotid aneurysm model in vivo.Results: Macrophages stimulated with CSE expressed significantly higher levels of nuclear factor of activated T-cells cytoplasmic 1 (NFATcl), TRAP, cathepsin K, matrix metalloproteinase-9 and membrane-type metalloproteinase (MT1-MMP). CSE-treated mouse aneurysms showed increased aneurysm size with increased TPM infiltration and protease expression compared to non-CSE-treated mouse aneurysms.Conclusions: These results suggest that CSE intensifies OCG in macrophages and promotes arterial aneurysmal progression.

Smoking and the Pathophysiology of Peripheral Artery Disease

“…At present, the pathogenesis of AAA is mainly attributed to inflammatory cell infiltration, the destruction of elastin and collagen in the media and adventitia, biological changes in smooth muscle cells and angiogenesis (180,181). Studies have confirmed that cigarette extracts induce the conversion of macrophages to osteoclasts through the classic RANKL-RANK pathway, upregulate the expression of NFATc1, promote macrophage activation, and induce the expression of the osteoclastogenesis-related proteases TRAP, cathepsin K and MMP-9 (129)(130)(131). Second, CSE also enhances the inflammatory response through the NF-kB pathway, which leads to the activation of macrophages and increased expression of MCP-1, MMP-9, IL-8, and TNF-α.…”

Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways

“… 13 TRAP-positive macrophages produce various matrix metalloproteinases (MMPs) such as MMP-2 (gelatinase A), MMP-9 (gelatinase B), MMP-12 (macrophage metalloelastase), and MMP-14 (MT1-MMP). 14 , 15 Therefore, TRAP-positive lung macrophages might display some molecular signatures of osteoclast differentiation regulated by the RANKL signaling pathway.…”

Unpacking the Complexities of a Silent Killer

“…In AAAs, we found that approximately 50% of macrophages form RANKL–RANK complexes on the cell surface that trigger activation of nuclear factor of activated T cells c1 (NFATc1) and expression of OC-related genes including MMP-9. Previous research in a mouse model has shown that cigarette smoke extract (CSE) treatment significantly exacerbates OCL macrophages and AAA formation, accompanied by upregulation of hypoxia-inducible factor-1 alpha [ 28 ].…”