Faculty Collaboration Database

Engagement of the Lewis X antigen (CD15) results in monocyte activation. Blood 1997 Jan 01;89(1):307-14

Date

01/01/1997

Pubmed ID

8978306

Scopus ID

2-s2.0-0031019583 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

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.

Author List

Lo SK, Golenbock DT, Sass PM, Maskati A, Xu H, Silverstein RL

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antibodies, Monoclonal
Cell Line
Cell Nucleus
Endothelium, Vascular
Gene Expression Regulation
Genes, Reporter
Humans
Immunoglobulin M
Immunologic Capping
Inflammation
Interleukin-1
Lewis X Antigen
Monocytes
Polymerase Chain Reaction
RNA, Messenger
Recombinant Fusion Proteins
Signal Transduction
Transcription Factors
Transfection
Tumor Necrosis Factor-alpha