Increased Procollagen III Aminoterminal Peptide-related Antigens and Fibroblast Growth Signals in the Lungs of Patients with Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder characterized by an increased density of inflammatory cells, fibroblasts, and collagen within the lung parenchyma. To gain insights into the mechanisms leading to the increased density of fibroblasts and altered collagen metabolism in the IPF lung, bronchoalveolar lavage fluid from normal subjects and patients with IPF or sarcoidosis was analyzed for (1) the presence of antigenic material related to the aminoterminal propeptide domain of type III procollagen, and (2) fibroblast growth-promoting activity in the extracellular milieu of the lower respiratory tract. Whereas bronchoalveolar lavage fluid (BALF) type III procollagen aminoterminal peptide-related antigen levels in 59 patients with sarcoidosis were similar to the levels of control subjects (p greater than 0.10), 31 patients with IPF had markedly increased levels (12-fold over controls; p less than 0.025, IPF versus controls; p less than 0.01, IPF versus sarcoidosis). Type III procollagen aminoterminal peptide-related antigen levels correlated with an increase in the ability of BALF to stimulate fibroblast proliferation (p less than 0.05). Furthermore, BALF from patients with IPF markedly stimulated human lung fibroblast proliferation in vitro (199% increase, p less than 0.01), whereas lavage fluid from patients with sarcoidosis and from control subjects did not. The enhanced fibroblast proliferation induced by IPF BALF occurred in the absence of serum and exogenous growth factors, suggesting that both competence- and progression-type growth factors were present in the lavage fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenetic and Clinical Significance of Fibroblast Activation in Scleroderma Lung Disease

“…This confirms a previously published study showing increased chemoattractant ac tivity of BAL fluid from patients with idiopathic pulmo nary fibrosis and a smaller group of patients with FA due to systemic sclerosis [ 19], Moreover, in this study, procol lagen III peptide was detectable in native BAL fluid from patients with FA but not from control subjects. This find ing in SSC patients is in accordance with other investiga tors who reported elevated procollagen III peptide levels in BAL fluid or epithelial lining fluid from patients with idiopathic pulmonary fibrosis [16,17,36] or sarcoidosis [15,18], Both, CAA and procollagen III peptide measure ments may serve as indicators of Fibroblast activation in the human lung in vivo.…”

“…Thus, the effect of BAL fluid on fibroblasts in vitro may provide relevant information on fibroblasts in vivo. Following this reasoning, Cantin et al [17] have examined BAL fluids for fibroblast growth pro moting activity. They found stimulatory activity in BAL fluids from patients with idiopathic pulmonary fibrosis but not in fluids from controls or sarcoidosis patients.…”

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

“…It may also be the result of cryptogenic processes [142][143][144]. In these diseases, fibrosis shares common characteristics, including fibroblast proliferation and extracellular matrix deposition [145][146][147].…”

N-Terminal Propetide of Type III Collagen in Tracheal Fluid and Serum in Preterm Infants at Risk for Bronchopulmonary Dysplasia

“…Our hypothesis was that PIIINP, reflecting the synthesis of type 111 collagen, would be such a marker. In adults, PIIINP levels have been found to be elevated in alveolar fluid in patients with idiopathic pulmonary fibrosis (16) and in serum and bronchoalveolar lavage fluid in patients with adult RDS (17) known to be complicated with severe fibrosis. In infants with advanced chronic lung disease, the ratio of type I/III collagen has been reported to be elevated, mainly because of elevated amounts of type I collagen in the lungs (1 8).…”