Evidence for IL-12-activated Ca2+ and tyrosine signaling pathways in human neutrophils.
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.
Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
K
K
Collison
S
S
Saleh
R
R
Parhar
B
B
Meyer
A
A
Kwaasi
K
K
Al-Hussein
S
S
Al-Sedairy
F
F
Al-Mohanna
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism / Q000502:physiology*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism* / Q000502:physiology
D000199:Actins; D011108:Polymers; D018664:Interleukin-12; D014443:Tyrosine; D002118:Calcium