PMID- 22985792
OWN - NLM
STAT- MEDLINE
DCOM- 20130402
LR  - 20220330
IS  - 1743-8977 (Electronic)
IS  - 1743-8977 (Linking)
VI  - 9
DP  - 2012 Sep 18
TI  - Enhancement of proinflammatory and procoagulant responses to silica particles by 
      monocyte-endothelial cell interactions.
PG  - 36
LID - 10.1186/1743-8977-9-36 [doi]
AB  - BACKGROUND: Inorganic particles, such as drug carriers or contrast agents, are 
      often introduced into the vascular system. Many key components of the in vivo 
      vascular environment include monocyte-endothelial cell interactions, which are 
      important in the initiation of cardiovascular disease. To better understand the 
      effect of particles on vascular function, the present study explored the direct 
      biological effects of particles on human umbilical vein endothelial cells 
      (HUVECs) and monocytes (THP-1 cells). In addition, the integrated effects and 
      possible mechanism of particle-mediated monocyte-endothelial cell interactions 
      were investigated using a coculture model of HUVECs and THP-1 cells. Fe(3)O(4) and 
      SiO(2) particles were chosen as the test materials in the present study. RESULTS: 
      The cell viability data from an MTS assay showed that exposure to Fe(3)O(4) or SiO(2) 
      particles at concentrations of 200 mug/mL and above significantly decreased the 
      cell viability of HUVECs, but no significant loss in viability was observed in 
      the THP-1 cells. TEM images indicated that with the accumulation of SiO(2) 
      particles in the cells, the size, structure and morphology of the lysosomes 
      significantly changed in HUVECs, whereas the lysosomes of THP-1 cells were not 
      altered. Our results showed that reactive oxygen species (ROS) generation; the 
      production of interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1 
      (MCP-1), tumor necrosis factor (TNF)-alpha and IL-1beta; and the expression of CD106, 
      CD62E and tissue factor in HUVECs and monocytes were significantly enhanced to a 
      greater degree in the SiO(2)-particle-activated cocultures compared with the 
      individual cell types alone. In contrast, exposure to Fe(3)O(4) particles had no 
      impact on the activation of monocytes or endothelial cells in monoculture or 
      coculture. Moreover, using treatment with the supernatants of 
      SiO(2)-particle-stimulated monocytes or HUVECs, we found that the enhancement of 
      proinflammatory response by SiO(2) particles was not mediated by soluble factors 
      but was dependent on the direct contact between monocytes and HUVECs. 
      Furthermore, flow cytometry analysis showed that SiO(2) particles could markedly 
      increase CD40L expression in HUVECs. Our data also demonstrated that the 
      stimulation of cocultures with SiO(2) particles strongly enhanced c-Jun 
      NH2-terminal kinase (JNK) phosphorylation and NF-kappaB activation in both HUVECs and 
      THP-1 cells, whereas the phosphorylation of p38 was not affected. CONCLUSIONS: 
      Our data demonstrate that SiO(2) particles can significantly augment 
      proinflammatory and procoagulant responses through CD40-CD40L-mediated 
      monocyte-endothelial cell interactions via the JNK/NF-kappaB pathway, which suggests 
      that cooperative interactions between particles, endothelial cells, and monocytes 
      may trigger or exacerbate cardiovascular dysfunction and disease, such as 
      atherosclerosis and thrombosis. These findings also indicate that the 
      monocyte-endothelial cocultures represent a sensitive in vitro model system to 
      assess the potential toxicity of particles and provide useful information that 
      may help guide the future design and use of inorganic particles in biomedical 
      applications.
FAU - Liu, Xin
AU  - Liu X
AD  - Shanghai Biomaterials Research & Testing Center, Shanghai Key Laboratory of 
      Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of 
      Medicine, No. 427 Ju-men Road, Shanghai 200023, China.
FAU - Xue, Yang
AU  - Xue Y
FAU - Ding, Tingting
AU  - Ding T
FAU - Sun, Jiao
AU  - Sun J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120918
PL  - England
TA  - Part Fibre Toxicol
JT  - Particle and fibre toxicology
JID - 101236354
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Ferric Compounds)
RN  - 0 (NF-kappa B)
RN  - 0 (Particulate Matter)
RN  - 1K09F3G675 (ferric oxide)
RN  - 7631-86-9 (Silicon Dioxide)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Antigens, CD/metabolism
MH  - Biomarkers/metabolism
MH  - Cell Adhesion/drug effects/physiology
MH  - Cell Communication/drug effects/physiology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytokines/*metabolism
MH  - Ferric Compounds/toxicity
MH  - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism/ultrastructure
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Lysosomes/drug effects/ultrastructure
MH  - Macrophages/*drug effects/metabolism/ultrastructure
MH  - NF-kappa B/metabolism
MH  - Particulate Matter/*toxicity
MH  - Signal Transduction
MH  - Silicon Dioxide/*toxicity
MH  - Thromboplastin/*metabolism
PMC - PMC3502427
EDAT- 2012/09/19 06:00
MHDA- 2013/04/03 06:00
PMCR- 2012/09/18
CRDT- 2012/09/19 06:00
PHST- 2012/02/25 00:00 [received]
PHST- 2012/09/11 00:00 [accepted]
PHST- 2012/09/19 06:00 [entrez]
PHST- 2012/09/19 06:00 [pubmed]
PHST- 2013/04/03 06:00 [medline]
PHST- 2012/09/18 00:00 [pmc-release]
AID - 1743-8977-9-36 [pii]
AID - 10.1186/1743-8977-9-36 [doi]
PST - epublish
SO  - Part Fibre Toxicol. 2012 Sep 18;9:36. doi: 10.1186/1743-8977-9-36.