Abstract
Fibrocytes are fibroblast-like cells, which appear to participate in wound healing and are present in pathological lesions associated with asthma, pulmonary fibrosis, and scleroderma. Fibrocytes differentiate from CD14+ peripheral blood monocytes, and the presence of serum delays this process dramatically. We previously purified the factor in serum, which inhibits fibrocyte differentiation, and identified it as serum amyloid P (SAP). As SAP binds to Fc receptors for immunoglobulin G (IgG; Fc gammaRs), Fc gammaR activation may be an inhibitory signal for fibrocyte differentiation. Fc gammaR are activated by aggregated IgG, and we find aggregated but not monomeric, human IgG inhibits human fibrocyte differentiation. Monoclonal antibodies that bind to Fc gammaRI (CD64) or Fc gammaRII (CD32) also inhibit fibrocyte differentiation. Aggregated IgG lacking Fc domains or aggregated IgA, IgE, or IgM do not inhibit fibrocyte differentiation. Incubation of monocytes with SAP or aggregated IgG inhibited fibrocyte differentiation. Using inhibitors of protein kinase enzymes, we show that Syk- and Src-related tyrosine kinases participate in the inhibition of fibrocyte differentiation. These observations suggest that fibrocyte differentiation can occur in situations where SAP and aggregated IgG levels are low, such as the resolution phase of inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / pharmacology
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Biopolymers / pharmacology
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Cell Differentiation / drug effects
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Cells, Cultured / cytology
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Cells, Cultured / drug effects
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Fibroblasts / cytology
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Fibroblasts / drug effects*
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Humans
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Immunoglobulin A / immunology
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Immunoglobulin A / pharmacology
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Immunoglobulin E / immunology
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Immunoglobulin E / pharmacology
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Immunoglobulin Fc Fragments / immunology
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Immunoglobulin G / immunology
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Immunoglobulin G / pharmacology*
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Immunoglobulin M / immunology
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Immunoglobulin M / pharmacology
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
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Intracellular Signaling Peptides and Proteins / physiology
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Monocytes / cytology
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Monocytes / drug effects*
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Phosphorylation
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Protein Processing, Post-Translational
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / physiology*
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Receptors, IgG / antagonists & inhibitors
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Receptors, IgG / immunology
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Receptors, IgG / physiology
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Serum Amyloid P-Component / physiology
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Syk Kinase
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / physiology
Substances
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Antibodies, Monoclonal
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Biopolymers
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Immunoglobulin A
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Immunoglobulin Fc Fragments
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Immunoglobulin G
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Immunoglobulin M
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Intracellular Signaling Peptides and Proteins
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Receptors, IgG
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Serum Amyloid P-Component
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polymeric IgA
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polymeric IgG
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polymeric IgM
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Immunoglobulin E
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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src-Family Kinases