title: Platelets induce a proinflammatory phenotype in monocytes via the CD147 pathway in rheumatoid arthritis.
abstract: BACKGROUND
  Activated platelets exert a proinflammatory action that can be largely ascribed to their ability to interact with monocytes. However, the mechanisms that promote dynamic changes in monocyte subsets in rheumatoid arthritis (RA) have not been clearly identified. The aim of this study was to determine whether platelet activation and the consequent formation of monocyte-platelet aggregates (MPA) might induce a proinflammatory phenotype in circulating monocytes in RA.
  
  
  METHODS
  The surface phenotype of platelets and the frequencies of monocyte subpopulations in the peripheral blood of RA patients were determined using flow cytometry. Platelets were sorted and co-cultured with monocytes. In addition, monocyte activation was assessed by measuring the nuclear factor κB (NF-κB) pathway. The disease activity was evaluated using the 28-joint disease activity score.
  
  
  RESULTS
  Platelet activation, circulating intermediate monocytes (Mon2) and MPA formation were significantly elevated in RA, especially in those with active disease status. Furthermore, Mon2 monocytes showed higher CD147 expression and responded to direct cell contact with activated platelets with higher cytokine production and matrix metallopeptidase 9 (MMP-9) secretion, which increased the expression of CD147. After the addition of specific antibodies for CD147, those effects were abolished. Furthermore, the NF-κB-driven inflammatory pathway may be involved in this process.
  
  
  CONCLUSIONS
  These findings indicate an important role of platelet activation and the consequent formation of MPA in the generation of the proinflammatory cytokine milieu and for the promotion and maintenance of the pathogenically relevant Mon2 monocyte compartment in RA, which is likely to play an important role in the pathogenesis of autoimmunity.
authors.forename: Meng-yao
authors.initials: MY
authors.lastname: Rong
authors.forename: Cong-hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Zhen-biao
authors.initials: ZB
authors.lastname: Wu
authors.forename: Wen
authors.initials: W
authors.lastname: Zeng
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Zheng
authors.forename: Qing
authors.initials: Q
authors.lastname: Han
authors.forename: Jun-feng
authors.initials: JF
authors.lastname: Jia
authors.forename: Xue-yi
authors.initials: XY
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051926:Basigin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: C497886:BSG protein, human; D018836:Inflammation Mediators; D051926:Basigin