Surfactant-associated proteins (SP-A, SP-B) are increased proportionally to alveolar phospholipids in sheep silicosis

Abstract

In silicosis, a profile of surfactant overproduction associated with type II epithelial cell hypertrophy and hyperplasia has been documented. In addition, enhanced accumulation of surfactant-associated protein A (SP-A) has been seen in the rat model of acute silicosis by 2 independent groups, but the exact role of these surfactant changes in silicosis are incompletely understood. In this study we measured in lung lavage surfactant total phospholipids and surfactant-associated proteins A and B (SP-A, SP-B). In addition, the surface tension reducing activities of lipid extracts of bronchoalveolar lavage fluids (BALFs) in the sheep silicosis model were examined using a pulsating bubble surfactometer. Two groups of animals (n = 18) were investigated: a saline-exposed (PBS-PBS) group and a silica-exposed (Si-PBS) group. Total surfactant phospholipids in the silicotic sheep increased 2-fold over the control sheep values (p < 0.05), as previously reported. In addition, we found a substantial rise in total surfactant-associated proteins, with significant increase in SP-A (1.16 +/- 0.22 micrograms/ml Si-PBS group vs. 0.70 +/- 0.07 micrograms/ml PBS-PBS group, p < 0.05) and a parallel but not significant increase in SP-B (2.68 +/- 0.90 micrograms/ml Si-PBS group vs. 1.10 +/- 0.30 micrograms/ml PBS-PBS group). The surface-tension-reducing activities of alveolar fluid lipid extracts did not differ significantly between the groups (Si-PBS group at maximal bubble radius [Rmax]: 27.0 +/- 1.6 and at minimal bubble radius [Rmin]: 1.0 +/- 0.7 milli Newton/m, vs. PBS-PBS group Rmax: 27.0 +/- 2.2 and Rmin: 0.7 +/- 0.3 milli Newton/m at 4 min pulsation). The ratios of SP-A and SP-B to lipid phosphorus levels document a proportional enhancement of surfactant-associated proteins and phospholipids, thus suggesting a co-ordinated upregulation of both surfactant-associated proteins and phospholipids in this model of silicosis. However, on an individual basis, these changes were not related, suggesting a more complex model of regulation. This study documents significant increases of the surfactant apoproteins proportional to changes in phospholipids in the lung of silicotic sheep. In spite of these alterations of surfactant components, organic solvent lipid extracts of BAPLFs surfactant remained equally effective in reducing surface tension.

Surfactant Protein A Modulates the Inflammatory Response in Macrophages during Tuberculosis

“…Some investigators have postulated that increased levels of SP-A are associated with increased susceptibility to TB. This hypothesis is based on studies which showed that there were increased SP-A levels in subjects with silicosis, pulmonary alveolar proteinosis, and HIV, three diseases in which there is increased susceptibility to mycobacterial infection (8,16,35,36). Recent data have extended these observations, and polymorphisms in the SP-A gene are associated with susceptibility to TB in certain populations (9).…”

“…Interestingly, patients with three diseases in which there is increased susceptibility to pulmonary mycobacterial infections, HIV, silicosis, and alveolar proteinosis, all have increased levels of SP-A in the bronchoalveolar lavage (BAL) fluid (BALF) (8,16,35,36). However, there is little data on the status of SP-A levels in patients with TB and how these levels change in response to therapy.…”

Surfactant protein A suppresses reactive nitrogen intermediates by alveolar macrophages in response to Mycobacterium tuberculosis

“…Another pulmonary disorder associated with elevated levels of SP-A is silicosis (70), a condition associated with a lifelong predisposition to tuberculosis (71). The mechanisms for the elevation of SP-A in silicosis are unclear, but this may represent a compensatory mechanism by the lung to facilitate clearance of silica particles from the lower respiratory tract.…”

Pulmonary epithelial cell expression of GM-CSF corrects the alveolar proteinosis in GM-CSF-deficient mice.

“…Cells were removed by centrifugation at 6,300 g for 10 min, and aliquots were stored at Ϫ 20 Њ C until analysis. SP-B was measured by ELISA as previously described (27). SP-A was measured using ELISA rabbit anti-mouse SP-A antiserum.…”