Idiopathic Pulmonary Fibrosis: Abnormalities in the Bronchoalveolar Lavage Content of Surfactant Protein A

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the lung characterized by an inflammatory infiltrate, alveolar type II cell hypertrophy and hyperplasia, and ultimate parenchymal scarring. The phospholipid composition of the surface-active material recovered by bronchoalveolar lavage (BAL) is abnormal in this disease. In the present study we have extended the analysis of surfactant components in IPF to include the major surfactant-associated protein, surfactant protein A (SP-A). SP-A has been reported to be essential for the formation of tubular myelin, to facilitate the adsorption of phospholipid to the air/liquid interface, and to stimulate uptake and inhibit secretion of surfactant in vitro. The BAL of 25 normal volunteers and 42 patients with interstitial lung disease (ILD) was analyzed for surfactant protein A content by ELISA and for phospholipids. The changes in BAL components were correlated to histopathologic markers at open-lung biopsy, clinical status, and survival. The total phospholipid (PL) recovered at lavage was reduced in patients with IPF relative to normal volunteers (p less than 0.0005). In addition, the percentage of phosphatidyl-glycerol (% PG) was decreased in patients with IPF (p less than 0.0001), whereas the percentage of phosphatidylcholine that was saturated was not altered. The content of surfactant protein A in lavage was reduced, even when normalized for the total amount of surface-active material recovered (SP-A/PL) (p less than 0.007). The reduction in SP-A was not specific to IPF but also occurred in other interstitial lung diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

KL-6 and Surfactant Proteins A and D in Serum and Bronchoalveolar Lavage Fluid in Patients with Acute Eosinophilic Pneumonia

“…Increased KL-6 levels have been found in the BALF of patients with a fibrotic interstitial lung disease, such as IPF or sarcoidosis (7,14). On the other hand, SP-A or SP-D levels in BALF from patients with IPF or interstitial pneumonia with collagen vascular disease (CVD-IP) have been reported to be either reduced (25)(26)(27) or unchanged (28,29). Reduced or unchanged SP-A and SP-D levels in BALF from clinically stable patients with cystic fibrosis have also been reported, but increased levels have been found when the disease progressed as a result of infection (30,31).…”

Anionic Pulmonary Surfactant Phospholipids Inhibit Inflammatory Responses from Alveolar Macrophages and U937 Cells by Binding the Lipopolysaccharide-interacting Proteins CD14 and MD-2

“…In idiopathic pulmonary fibrosis, ARDS, and asthma, several groups reported decreased unsaturated PG in surfactant (18,(52)(53)(54)(55)(56)(57). The issues of cause and effect in the above diseases remain unclear, but any condition that results in reduced levels of unsaturated PG pools within the lung is likely to increase the susceptibility to inflammatory processes elicited through TLR4 activation.…”

Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability

“…Protein samples were separated by 8-16% SDS-PAGE and stained with Coomassie blue or silver (25). For immunoblot analysis, protein species were transferred to nitrocellulose membranes and reacted with rabbit polyclonal anti-hSP-A antibody (26) or anti-hSP-D antibody (a gift of E.C. Crouch, Washington University, St. Louis, Missouri, USA).…”