Aggregated IgG inhibits the differentiation of human fibrocytes

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. Fi-brocytes differentiate from CD14 peripheral blood monocytes, and the presence of serum de-lays this process dramatically. We previously puri-fied the factor in serum, which inhibits fibrocyte differentiation, and identified it as serum amyloid P (SAP). As SAP binds to Fc receptors for immuno-globulin G (IgG; FcRs), FcR activation may be an inhibitory signal for fibrocyte differentiation. FcR are activated by aggregated IgG, and we find aggregated but not monomeric, human IgG inhibits human fibrocyte differentiation. Monoclonal anti-bodies that bind to FcRI (CD64) or FcRII (CD32) also inhibit fibrocyte differentiation. Ag-gregated IgG lacking Fc domains or aggregated IgA, IgE, or IgM do not inhibit fibrocyte differen-tiation. Incubation of monocytes with SAP or ag-gregated 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 differenti-ation. 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. J. Leukoc. Biol