title: The long pentraxin PTX3 promotes fibrocyte differentiation.
abstract: Monocyte-derived, fibroblast-like cells called fibrocytes are associated with fibrotic lesions. The plasma protein serum amyloid P component (SAP; also known as pentraxin-2, PTX2) inhibits fibrocyte differentiation in vitro, and injections of SAP inhibit fibrosis in vivo. SAP is a member of the pentraxin family of proteins that includes C-reactive protein (CRP; PTX1) and pentraxin-3 (PTX3). All three pentraxins are associated with fibrosis, but only SAP and CRP have been studied for their effects on fibrocyte differentiation. We find that compared to SAP and CRP, PTX3 promotes human and murine fibrocyte differentiation. The effect of PTX3 is dependent on FcγRI. In competition studies, the fibrocyte-inhibitory activity of SAP is dominant over PTX3. Binding competition studies indicate that SAP and PTX3 bind human FcγRI at different sites. In murine models of lung fibrosis, PTX3 is present in fibrotic areas, and the PTX3 distribution is associated with collagen deposition. In lung tissue from pulmonary fibrosis patients, PTX3 has a widespread distribution, both in unaffected tissue and in fibrotic lesions, whereas SAP is restricted to areas adjacent to vessels, and absent from fibrotic areas. These data suggest that the relative levels of SAP and PTX3 present at sites of fibrosis may have a significant effect on the ability of monocytes to differentiate into fibrocytes.
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Darrell
authors.initials: D
authors.lastname: Pilling
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Nehemiah
authors.initials: N
authors.lastname: Cox
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America.
authors.forename: Varsha
authors.initials: V
authors.lastname: Vakil
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, United States of America; Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gomer
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D017452:Receptors, IgG / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D017452:Receptors, IgG; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C489017:FCGR1A protein, human; C485701:Fcgr1 protein, mouse