B activation but not for phagocytosis
Immunology Department, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City
Correspondence: Dr. Carlos Rosales, Department of Immunology, Instituto de Investigaciones BiomédicasUNAM, Apto. Postal 70228, Cd. Universitaria, México D.F.-04510, Mexico. E-mail: carosal{at}servidor.unam.mx
The molecular events that transduce signals from Fc receptors to
the various cellular responses are still poorly defined. We have
investigated the role of phosphatidylinositol 3-kinase (PI 3-K) and
extracellular signal-regulated kinase (ERK) in gene activation and
phagocytosis in monocytes. In the THP-1 monocytic cell line,
cross-linking of Fc receptors by immune complexes results in activation
of the transcription factor NF-
B, via activation of ERK. Activation
of both ERK and NF-
B was blocked by wortmannin and LY294002,
specific inhibitors of PI 3-K. Wortmannin also inhibited the Fc
receptor-mediated increase in the cytosolic calcium concentration, but
it did not block immunoglobulin G (IgG)-mediated phagocytosis. In
addition, the ERK inhibitor PD98059 did not block phagocytosis of
IgG-coated erythrocytes. Both the increase in the cytosolic calcium
concentration and phagocytosis depend on an active actin cytoskeleton,
as indicated by the total lack of both responses after treatment with
cytochalasin B. In contrast, cytochalasin B did not affect Fc
receptor-mediated activation of NF-
B. These results identify PI 3-K
and ERK as important signaling molecules in the Fc receptor signal
transduction pathway of monocytes, which leads to the nucleus for gene
activation. These results also suggest that, in contrast to other cell
types, unstimulated monocytes do not require PI 3-K and ERK for
phagocytosis.
Key Words: monocytes signal transduction Fc receptors
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