Evidence for IL-12-activated Ca2+ and tyrosine signaling pathways in human neutrophils
K Collison, S Saleh, R Parhar, B Meyer… - The Journal of …, 1998 - journals.aai.org
K Collison, S Saleh, R Parhar, B Meyer, A Kwaasi, K Al-Hussein, S Al-Sedairy…
The Journal of Immunology, 1998•journals.aai.orgThe cytokine IL-12 is proposed to play a bridging role between innate and adaptive
immunity. Here we demonstrate that IL-12 binds specifically to human neutrophils. This
binding leads to a transient increase in 1) intracellular free calcium due to its release from
membrane-enclosed stores and its influx from extracellular medium, 2) actin polymerization,
and 3) tyrosine phosphorylation. IL-12 treatment also leads to a concentration-dependent
increase in reactive oxygen metabolite production. The effect of IL-12 is blocked by …
immunity. Here we demonstrate that IL-12 binds specifically to human neutrophils. This
binding leads to a transient increase in 1) intracellular free calcium due to its release from
membrane-enclosed stores and its influx from extracellular medium, 2) actin polymerization,
and 3) tyrosine phosphorylation. IL-12 treatment also leads to a concentration-dependent
increase in reactive oxygen metabolite production. The effect of IL-12 is blocked by …
Abstract
The cytokine IL-12 is proposed to play a bridging role between innate and adaptive immunity. Here we demonstrate that IL-12 binds specifically to human neutrophils. This binding leads to a transient increase in 1) intracellular free calcium due to its release from membrane-enclosed stores and its influx from extracellular medium, 2) actin polymerization, and 3) tyrosine phosphorylation. IL-12 treatment also leads to a concentration-dependent increase in reactive oxygen metabolite production. The effect of IL-12 is blocked by neutralizing Abs to IL-12. Inhibition of either calcium transient or tyrosine phosphorylation causes inhibition of reactive oxygen metabolite production. However, inhibition of actin polymerization enhances IL-12-induced oxidase activation. Our data suggest 1) a direct role for IL-12 in the activation of human neutrophils, and 2) a calcium-dependent signaling pathway for IL-12.
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