Pulmonary surfactant proteins and lipids as modulators of inflammation and innate immunity

The pulmonary surfactant system of the human lung consists of unique lipids and proteins that contribute to the biophysical and innate immune properties of the organ. Surfactant protein A (SP-A) is an oligomeric protein consisting of 18 protomers with collagen and lectin-like domains that recognizes glycoconjugates, lipids and protein determinants on both host cells and invading microorganisms. The authors examined the interaction of SP-A with Mycoplasma pneumoniae and the influence of the protein upon the innate immune response to the bacteria.

The authors quantified SP-A interaction with bacteria using ELISA, and identified the major surface ligand by thin layer chromatography, HPLC and mass spectrometry. The inflammatory response of human and rat macrophages was measured by quantifying tumour necrosis factor-alpha secretion using ELISA, and nitric oxide production.

SP-A bound the bacteria with high affinity and enhanced the inflammatory response of human and rat macrophages to the organism and its membranes. Analysis of the interaction of SP-A with the bacteria revealed that the major ligand was a phospholipid. The lipid ligand was purified by a combination of thin layer and HPLC, and identified by mass spectrometry. The mass spectrometry demonstrated that the SP-A reactive lipid consisted of several disaturated molecular species of phosphatidylglycerol (PtdGro). Additional experiments were performed to determine if disaturated PtdGro was capable of interfering with the action of SP-A as an inhibitor of bacterial lipopolysaccharide-induced inflammatory mediator production by macrophages. The disaturated PtdGro failed to alter the anti-inflammatory action of SP-A but unexpectedly these same studies revealed that unsaturated PtdGro can modify the host response to lipopolysaccharide.

These findings reveal that both the lipids and proteins of pulmonary surfactant play a role in regulating the host response to invading microorganisms.