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Originally published online as doi:10.1189/jlb.0805456 on March 16, 2006

Published online before print March 16, 2006
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(Journal of Leukocyte Biology. 2006;79:1242-1251.)
© 2006 by Society for Leukocyte Biology

Aggregated IgG inhibits the differentiation of human fibrocytes

Darrell Pilling1, Nancy M. Tucker and Richard H. Gomer

Department of Biochemistry and Cell Biology, Rice University, Houston, Texas

1Correspondence: Department of Biochemistry and Cell Biology, MS-140, Rice University, Houston, TX 77005-1892. E-mail: dpilling{at}bioc.rice.edu

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{gamma}Rs), Fc{gamma}R activation may be an inhibitory signal for fibrocyte differentiation. Fc{gamma}R are activated by aggregated IgG, and we find aggregated but not monomeric, human IgG inhibits human fibrocyte differentiation. Monoclonal antibodies that bind to Fc{gamma}RI (CD64) or Fc{gamma}RII (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.

Key Words: monocytes • inflammation • cellular differentiation • serum amyloid P • Fc{gamma}R




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