Engagement of the Lewis X antigen (CD15) results in monocyte activation

Blood. 1997 Jan 1;89(1):307-14.


We previously reported that monocyte adhesion to tumor necrosis factor-alpha (TNF-alpha)-treated endothelial cells increased expression of tissue factor and CD36 on monocytes. Using immunological cross-linking to mimic receptor engagement by natural ligands, we now show that CD15 (Lewis X), a monocyte counter-receptor for endothelial selectins may participate in this response. We used cytokine production as a readout for monocyte activation and found that CD15 cross-linking induced TNF-alpha release from peripheral blood monocytes and cells from the monocytic cell line MM6. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in steady-state TNF-alpha mRNA after 3 to 4 hours of cross-linking. CD15 cross-linking also concomitantly increased interleukin-1 beta (IL-1 beta) mRNA, while no apparent change was observed in the levels of beta-actin mRNA, indicating specificity. To examine transcriptional regulation of cytokine genes by CD15 engagement, a CAT plasmid reporter construct containing IL-1 beta promoter/enhancer sequences was introduced into MM6. Subsequent cross-linking of CD15 increased CAT activity. CD15 engagement by monoclonal antibody also attenuated IL-1 beta transcript degradation, demonstrating that signaling via CD15 also had posttranscriptional effects. Nuclear extracts of anti-CD15 cross-linked cells demonstrated enhanced levels of the transcriptional factor activator protein-1, minimally changed nuclear factor-kappa B, and did not affect SV40 promoter specific protein-1. We conclude that engagement of CD15 on monocytes results in monocyte activation. In addition to its well-recognized adhesive role, CD15 may function as an important signaling molecule capable of initiating proinflammatory events in monocytes that come into contact with activated endothelium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Cell Line
  • Cell Nucleus / metabolism
  • Endothelium, Vascular / cytology
  • Gene Expression Regulation / drug effects*
  • Genes, Reporter
  • Humans
  • Immunoglobulin M / pharmacology
  • Immunologic Capping
  • Inflammation / physiopathology
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism*
  • Lewis X Antigen / physiology*
  • Monocytes / physiology*
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / biosynthesis
  • Signal Transduction / physiology
  • Transcription Factors / metabolism
  • Transfection
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Antibodies, Monoclonal
  • Immunoglobulin M
  • Interleukin-1
  • Lewis X Antigen
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Tumor Necrosis Factor-alpha