Abstract
Human C-reactive protein (CRP) at acute phase levels of 10-200 microg/ml triggered the phosphorylation of FcgammaRIIa, Syk kinase, and phospholipase Cgamma2 in granulocytic HL-60 cells. CRP also stimulated translocation to the membrane of both phospholipase Cgamma2 and phosphatidylinositol-3-kinase. The signaling response triggered by CRP was a rapid, early event with kinetics similar to the response elicited by human IgG. Both soluble-aggregated CRP and monomeric CRP cross-linked FcgammaRII to generate a signal of the same intensity. The results are consistent with signaling through the intrinsic immunoreceptor tyrosine-based activation motif of the cytoplasmic domain of FcgammaRIIa, the major CRP-receptor on monocytes and neutrophils that is responsible for CRP-mediated phagocytosis. The signaling events driven by CRP have the potential to regulate infiltrating neutrophil activities.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Antigens, CD / metabolism
-
Antigens, CD / physiology*
-
C-Reactive Protein / physiology*
-
Calcium / metabolism
-
Calcium Signaling / immunology
-
Cell Membrane / enzymology
-
Cell Membrane / metabolism
-
Enzyme Precursors / metabolism
-
Granulocytes / enzymology
-
Granulocytes / immunology*
-
Granulocytes / metabolism*
-
HL-60 Cells
-
Humans
-
Intracellular Fluid / metabolism
-
Intracellular Signaling Peptides and Proteins
-
Isoenzymes / metabolism
-
Phosphatidylinositol 3-Kinases / metabolism
-
Phospholipase C gamma
-
Phosphorylation
-
Protein-Tyrosine Kinases / metabolism
-
Receptors, IgG / metabolism
-
Receptors, IgG / physiology*
-
Signal Transduction / immunology*
-
Syk Kinase
-
Type C Phospholipases / metabolism
-
src-Family Kinases / metabolism
Substances
-
Antigens, CD
-
Enzyme Precursors
-
Fc gamma receptor IIA
-
Intracellular Signaling Peptides and Proteins
-
Isoenzymes
-
Receptors, IgG
-
C-Reactive Protein
-
Phosphatidylinositol 3-Kinases
-
Protein-Tyrosine Kinases
-
SYK protein, human
-
Syk Kinase
-
src-Family Kinases
-
Type C Phospholipases
-
Phospholipase C gamma
-
Calcium