Functional role for the myeloid differentiation antigen CD14 in the activation of human monocytes by IL-2.
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.
Bosco
M C
MC
Intramural Research Support Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. mcbosco@tin.it
Espinoza-Delgado
I
I
Rowe
T K
TK
Malabarba
M G
MG
Longo
D L
DL
Varesio
L
L
D002448:Cell Adhesion; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D018076:DNA, Complementary; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors