Activation of the Complement System on Human Endothelial Cells by Urban Particulate Matter Triggers Inflammation-Related Protein Production

Abstract

Exposure to particulate matter (PM) is becoming a major global health issue. The amount and time of exposure to PM are known to be closely associated with cardiovascular diseases. However, the mechanism through which PM affects the vascular system is still not clear. Endothelial cells line the interior surface of blood vessels and actively interact with plasma proteins, including the complement system. Unregulated complement activation caused by invaders, such as pollutants, may promote endothelial inflammation. In the present study, we sought to investigate whether urban PM (UPM) acts on the endothelial environment via the complement system. UPM-treated human endothelial cells with normal human serum showed the deposition of membrane attack complexes (MACs) on the cell surface via the alternative pathway of the complement system. Despite the formation of MACs, cell death was not observed, and cell proliferation was increased in UPM-mediated complement activation. Furthermore, complement activation on endothelial cells stimulated the production of inflammation-related proteins. Our results revealed that UPM could activate the complement system in human endothelial cells and that complement activation regulated inflammatory reaction in microenvironment. These findings provide clues with regard to the role of the complement system in pathophysiologic events of vascular disease elicited by air pollution.

Mechanism of novel enoxaparin sodium high viscosity bone cement reducing thrombosis by regulating the expression of CD40 in endothelial cells

“…The complement system is composed of complement inherent components, complement regulatory proteins and complement receptors [29]. Some proteins in complement receptors are expressed in vascular endothelial cells [30], while CD40 is expressed in B cells, mononuclear macrophages, dendritic cells and vascular endothelial cells [31].Therefore, we found that ES-PMMA bone cement reduce local thrombosis by regulating vascular endothelial CD40 protein expression.…”

Double-Edged Sword: Exploring the Mitochondria–Complement Bidirectional Connection in Cellular Response and Disease

“…While ROS can serve as signaling molecules to activate the host defense system against pathogens, excessive ROS production can lead to oxidative damage [ 62 ]. Several prior studies indicate that oxidative stress damages cells, leading to the release of DAMPs which activates the extracellular complement system through all three pathways [ 17 , 63 , 64 ]. It was demonstrated that exposure of urban particulate matter to human umbilical vein endothelial cells enhances ROS production and subsequent activation of the complement system via the alternative pathway [ 64 ].…”

“…Several prior studies indicate that oxidative stress damages cells, leading to the release of DAMPs which activates the extracellular complement system through all three pathways [ 17 , 63 , 64 ]. It was demonstrated that exposure of urban particulate matter to human umbilical vein endothelial cells enhances ROS production and subsequent activation of the complement system via the alternative pathway [ 64 ]. This observation was confirmed by inhibiting ROS production, which suppresses expression of retinol-binding protein 4/RBP4 and c-reactive protein/CRP, which are biomarkers of inflammation, indicating inhibited complement activation [ 64 ].…”

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures

“…Inflammation is another critical mechanism affected by these pollutants [10,155,[175][176][177][178][179][180][181][182][183][184][185][186]. Chronic exposure to pollutants can trigger a sustained inflammatory response within the cardiovascular system and other organs as well.…”