Elevated Levels of Lung Surfactant Protein A in Sera from Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Alveolar Proteinosis

Abstract

An enzyme-linked immunosorbent assay using monoclonal antibodies to human lung surfactant protein A (SP-A) was applied to sera from patients with lung diseases. We examined whether SP-A appears in the sera of patients with diseases that are known to cause alterations in surfactant composition in bronchoalveolar lavage fluids, and we characterized the SP-A that was found. The level of SP-A in sera from 57 healthy volunteers was 45 +/- 3 ng/ml (mean +/- SEM). The levels in patients with idiopathic pulmonary fibrosis (IPF) (205 +/- 23 ng/ml, n = 32) and pulmonary alveolar proteinosis (PAP) (285 +/- 23 ng/ml, n = 6) were significantly higher than those in healthy control subjects (p < 0.01), whereas those of sarcoidosis (n = 16), pneumonia (n = 14), and tuberculosis (n = 14) were 52 +/- 27 ng/ml, 65 +/- 11 ng/ml, and 49 +/- 23 ng/ml, respectively. Electrophoresis and immunoblotting analysis demonstrated that the fraction isolated from serum of a patient with PAP or IPF by anti-SP-A immunoaffinity column chromatography consisted chiefly of human IgG and IgM, and that it also contained SP-A. Furthermore, IgG was found in preparation of purified human SP-A. SP-A was demonstrated to bind to nonimmune IgG coated onto microtiter wells. Gel filtration analysis revealed that serum SP-A was eluted at fractions of larger molecular size than was the purified SP-A. These findings suggest that SP-A appears in the bloodstream as a complex with immunoglobulin in IPF and in PAP.

Advances in the study of biomarkers of idiopathic pulmonary fibrosis in Japan

“…They are mainly produced by alveolar epithelial type II pneumocytes and Clara cells within the lungs. Elevated serum levels of SP-A in patients with IPF were first noted in 1993 (19). Serum levels of SP-A in patients with IPF and pulmonary alveolar proteinosis (PAP) were found to be significantly higher than those in healthy volunteers and patients with other non-interstitial lung diseases.…”

“…Levels of KL-6 in BALF were reported to be consistent with those in serum (5,8,9), whereas the levels of SP-A and SP-D in BALF were reported to be inversely correlated with levels in serum (19)(20)(21). Although the levels of KL-6, SP-A and SP-D in BALF are potential biomarkers for IPF, the inconvenience of obtaining BALF has resulted in their limited use clinically.…”

Identification of CD245 as myosin 18A, a receptor for surfactant A: A novel pathway for activating human NK lymphocytes

“…At the cell level, myosin 18A participates in cytoskeleton organization, 41 Golgi budding 32 and DNA-damaged-induced Golgi dispersion by its association with F-actin and Golgi Phosphoprotein 3 (GOLPH3) in epithelial cells 42 but its specific role in NK cells was not shown yet . Myosin 18A was also reported as a receptor for the surfactant protein A (SP-A), 17 a collectin present in human lung, 18 blood, 43 intestinal tract 44 and skin 45 that participates in the elimination of pathogens. 21 SP-A has also been shown to strongly stimulate the anti-tumor immunity in a xenograft mouse model.…”

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

“…Monoclonal antibody (mAb) against RSV protein F (B12) was produced as described previously [35,36]. Surfactant was isolated from bronchoalveolar lavage fluids of patients with alveolar proteinosis [37], and SP-A was purified from delipidated surfactant as described previously [4]. Human milk LF was purchased from Sigma (St. Louis, MO).…”