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PMID: 16543402 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Aggregated IgG inhibits the differentiation of human fibrocytes.

Journal of leukocyte biology ·Vol. 79 ·No. 6 ·2006-06-00 ·Pages 1242-51

Pilling D, Tucker NM, Gomer RH

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.

MeSH Terms
Antibodies, Monoclonal/pharmacology Biopolymers/pharmacology Cell Differentiation/drug effects Cells, Cultured/cytology,drug effects Fibroblasts/cytology,drug effects Humans Immunoglobulin A/immunology,pharmacology Immunoglobulin E/immunology,pharmacology Immunoglobulin Fc Fragments/immunology Immunoglobulin G/immunology,pharmacology Immunoglobulin M/immunology,pharmacology Intracellular Signaling Peptides and Proteins/antagonists & inhibitors,physiology Monocytes/cytology,drug effects Phosphorylation Protein Processing, Post-Translational Protein-Tyrosine Kinases/antagonists & inhibitors,physiology Receptors, IgG/antagonists & inhibitors,immunology,physiology Serum Amyloid P-Component/physiology Syk Kinase src-Family Kinases/antagonists & inhibitors,physiology
Chemicals
Antibodies, Monoclonal Biopolymers Immunoglobulin A Immunoglobulin Fc Fragments Immunoglobulin G Immunoglobulin M Intracellular Signaling Peptides and Proteins Receptors, IgG Serum Amyloid P-Component polymeric IgA polymeric IgG polymeric IgM Immunoglobulin E Protein-Tyrosine Kinases SYK protein, human Syk Kinase src-Family Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pilling Darrell
Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005-1892, USA. dpilling@bioc.rice.edu
Tucker Nancy M
Gomer Richard H
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Article Info
Journal
Journal of leukocyte biology
Abbr.
J Leukoc Biol
ISSN
0741-5400
DOI
10.1189/jlb.0805456
Email
dpilling@bioc.rice.edu
Published
2006-06-00
Epub
2006-00-16
Pages
1242-51
Language
English
Region
United States
NLM ID
8405628
PMCID
PMC4482138
Subset
IM
Grants
NHLBI NIH HHS · R01 HL083029 · United States
External Links
PubMed source DOI: 10.1189/jlb.0805456 PMC Full Text View journal details
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