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

Maria Caria Bosco, Igor Espinoza-Delgado, Tammy K. Rowe, Maria Grazia Malabarba, Dan L. Longo, Luigi Varesio

Research output: Contribution to journalArticle

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-γ-induced, monocyte tumoricidal activity. Furthermore, anti-CD14 mAbs effectively inhibited the secretion of IL-8 and IL-1β 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 β and γ 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-1β 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 1L-2.

Original languageEnglish
Pages (from-to)2922-2931
Number of pages10
JournalJournal of Immunology
Volume159
Issue number6
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Immunology

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