Deficient Hydrophilic Lung Surfactant Proteins A and D with Normal Surfactant Phospholipid Molecular Species in Cystic Fibrosis

Abstract

Chronic bacterial colonization of the lungs, with an excessive inflammatory response, is the major cause of morbidity and mortality in cystic fibrosis. Lung surfactant exhibits a spectrum of potential immunomodulatory properties: phospholipid components inhibit cellular inflammatory responses, whereas the hydrophilic surfactant proteins A (SP-A) and D (SP-D) are integral components of the innate host defense response of the lungs against bacterial infection. Consequently, alteration to the relative proportions of lung surfactant components may alter the susceptibility of the lungs to bacterial colonization. In this study, bronchoalveolar lavage (BAL) samples were collected at diagnostic fiberoptic bronchoscopy from 11 control children, 13 children with cystic fibrosis, and 11 children with acute lung infection. Electrospray ionization mass spectrometry analysis demonstrated negligible changes to the molecular species or total BAL concentrations of phosphatidylcholine, phosphatidylglycerol, or phosphatidylinositol among the three subject groups. In contrast, median SP-A concentration was decreased (P < 0.001) in the cystic fibrosis group (2.65 microg/ml) compared with control (12.35 microg/ml) and infection (9.76 microg/ml) groups. Median SP-D was also decreased (P < 0.05) in the infection (12.17 ng/ml) compared with the control group (641 ng/ml), and was below assay limits for the majority of cystic fibrosis children (P < 0. 001). This dramatic decrease of hydrophilic surfactant proteins in the presence of normal surfactant phospholipid may be one mechanism underlying the relative ineffectiveness of the cellular inflammatory response in killing invading bacteria in the lungs of patients with cystic fibrosis.

Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens

“…The selected dose of SP-A and SP-D was based on the physiological concentrations of these proteins reported in rodent lung lavage: the SP-A concentration in the rat lavage was 7.3 ± 0.8 µg/ml and the SP-D concentration in the lavage from C57Bl/6 mice 6-8 weeks of age was observed to be 552 ng/ml (16,17). For human lung lavage, the SP-A concentration ranges from 1 to 10 µg/ml and the SP-D concentration varies between 300 ng and 600 ng/ml (7,18).…”

SP-A1 and SP-A2 variants differentially enhance association ofPseudomonas aeruginosawith rat alveolar macrophages

“…In CF, the levels of SP-A and other surfactant components have been shown to be altered (20,29,53). Because SP-A enhances phagocytosis and SP-A variants have been identified with quantitative and qualitative differences, it is possible that the SP-A variant differences result in differences in their effectiveness to enhance association of P. aeruginosa with alveolar macrophages and thus may contribute to varied disease severity.…”

Pulmonary Surfactant Protein-A (SP-A) Restores the Surface Properties of Surfactant after Oxidation by a Mechanism That Requires the Cys6 Interchain Disulfide Bond and the Phospholipid Binding Domain

“…Mass Spectroscopy-Molecular species of surfactant PLs were analyzed by electrospray ionization mass spectroscopy (ESI-MS) with a triple quadrupole ESI-MS (model PI 365, Sciex Co., Concord, ON, Canada) using positive mode for PCs and negative mode for PGs employing a slight modification of the method of Postle et al (13,24). Briefly, the surfactant lipids were extracted with chloroform:methanol (1:1, v/v) by the method of Bligh and Dyer (25).…”