The long pentraxin PTX3 promotes fibrocyte differentiation.

Darrell Pilling,Nehemiah Cox,Varsha Vakil,J Sjef Verbeek,Richard H Gomer,Gernot Zissel

doi:10.1371/journal.pone.0119709

Darrell Pilling, Nehemiah Cox + Show 4 more

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https://doi.org/10.1371/journal.pone.0119709

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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.

Highlights

During fibrosis, some monocytes leave the circulation, enter the tissue, and differentiate into fibroblast-like cells called fibrocytes [1,2,3]
These data suggest that the relative levels of Serum Amyloid P component (SAP) and PTX3 present at sites of fibrosis may have a significant effect on the ability of monocytes to differentiate into fibrocytes
To determine if PTX3 is associated with human lung fibrosis, we examined the distribution of PTX3 in lung tissue from chronic obstructive pulmonary disease (COPD) patients with relatively normal lungs (> 80% Forced vital capacity (FVC)) and idiopathic pulmonary fibrosis (IPF) patients (

Summary

Introduction

Some monocytes leave the circulation, enter the tissue, and differentiate into fibroblast-like cells called fibrocytes [1,2,3]. Fibrocytes are found in lesions associated with fibrotic diseases such as pulmonary fibrosis, congestive heart failure, cirrhosis of the liver, and nephrogenic systemic fibrosis [3,7,8,9,10,11]. There are very few fibrocytes [3]. Fibrocyte differentiation is regulated by several factors including the plasma protein Serum Amyloid P component (SAP; PTX2) [3,5,12,13]. SAP is a pentameric protein that belongs to the pentraxin family of evolutionarily conserved proteins [14]. There are three main systemic pentraxins in mammals: SAP, C-reactive protein

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