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Functional role for the myeloid differentiation antigen CD14 in the activation of human monocytes by IL-2.

M C Bosco, I Espinoza-Delgado, T K Rowe, M G Malabarba, D L Longo and L Varesio
J Immunol September 15, 1997, 159 (6) 2922-2931;
M C Bosco
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I Espinoza-Delgado
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T K Rowe
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M G Malabarba
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D L Longo
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L Varesio
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Abstract

Human monocytes express functional IL-2Rs and are directly activated by IL-2 to exert effector and secretory functions. In this study, we demonstrate that the myeloid differentiation Ag CD14 participates in monocyte activation by IL-2. Engagement of CD14 by specific mAbs resulted in the selective and dose-dependent suppression of IL-2-induced, but not of IFN-gamma-induced, monocyte tumoricidal activity. Furthermore, anti-CD14 mAbs effectively inhibited the secretion of IL-8 and IL-1beta in response to IL-2. Preincubation of monocytes with mAbs directed to selected epitopes on CD14 blocked the binding of IL-2 to the cell surface, providing a possible explanation for the inhibition of IL-2-triggered responses. A critical role for CD14 in IL-2-mediated monocyte activation was further demonstrated by experiments with the human U937 promonocytic cell line. These cells are negative for CD14 and unresponsive to IL-2 despite the expression of the beta and gamma subunits of the IL-2R. U937 cells acquired the capacity to respond to IL-2 following transfection with the human CD14 cDNA (U937/CD14). Stimulation of U937/CD14 cells with IL-2 up-regulated the constitutive levels of IL-8 mRNA, whereas no change in IL-8 mRNA basal expression was observed in control cells transfected with the vector alone (U937/Neo). Accordingly, increased secretion of IL-8 by U937/CD14, but not by U937/Neo cells, was detected following exposure to IL-2. Expression of IL-1beta was also augmented by IL-2 in U937/CD14 cells. These data provide the first evidence that CD14 expression is required for the response of monocytic cells to IL-2.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 159, Issue 6
15 Sep 1997
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Functional role for the myeloid differentiation antigen CD14 in the activation of human monocytes by IL-2.
M C Bosco, I Espinoza-Delgado, T K Rowe, M G Malabarba, D L Longo, L Varesio
The Journal of Immunology September 15, 1997, 159 (6) 2922-2931;

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Functional role for the myeloid differentiation antigen CD14 in the activation of human monocytes by IL-2.
M C Bosco, I Espinoza-Delgado, T K Rowe, M G Malabarba, D L Longo, L Varesio
The Journal of Immunology September 15, 1997, 159 (6) 2922-2931;
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Print ISSN 0022-1767        Online ISSN 1550-6606