Human Monocytes - CD14, CD16 - Ziegler-Heitbrock

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

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. (C) 1997 by The American Society of Hematology.

Authors: Lo, S.K., Golenbock, D.T., Sass, P.M., Maskati, A., Xu, H., Silverstein, R.L.
Journal: Blood, 89: 307-314
Year: 1997
PubMed: Find in PubMed