Ja. Nick et al., ACTIVATION OF A P38 MITOGEN-ACTIVATED PROTEIN-KINASE IN HUMAN NEUTROPHILS BY LIPOPOLYSACCHARIDE, The Journal of immunology, 156(12), 1996, pp. 4867-4875
Stimulation of human neutrophils by LPS is central to the pathogenesis
of sepsis and the adult respiratory distress syndrome. The intracellu
lar signaling pathway that results in cellular responses following LPS
stimulation in neutrophils is unknown. We report that exposure of neu
trophils to LPS results in the phosphorylation and activation of a p38
mitogen-activated protein (MAP) kinase, occurring in a concentration-
dependent manner, with maximum response at 20 to 25 min. Partial purif
ication of a p38 MAP kinase by ion exchange chromatography established
it as distinct from the p42/p44 (extracellular signal-regulated kinas
es (ERK-1 and ERK-2) MAP kinases). Activation of the p38 MAP kinase by
LPS in human neutrophils occurs via CD14, a proposed LPS receptor, an
d requires the presence of plasma containing the LPS-binding protein.
This intracellular signaling pathway is independent of protein kinase
C and does not involve Raf, MAP/ERK kinase kinase-1, MAP/ERK kinase-1,
or MAP/ERK kinase-2 and does not result in the activation of the p42/
p44 ERK MAP kinases or the c-jun N-terminal kinases.