Surfactant phospholipid changes after antigen challenge: a role for phosphatidylglycerol in dysfunction

Abstract

In asthma, inflammation-mediated surfactant dysfunction contributes to increased airway resistance, but the mechanisms for dysfunction are not understood. To test mechanisms that alter surfactant function, atopic asthmatics underwent endobronchial antigen challenge and bronchoalveolar lavage (BAL). BAL fluids were sequentially separated into cells, surfactant, and supernatant, and multiple end points were analyzed. Each end point's unique relationship to surfactant dysfunction was determined. Our results demonstrate that minimum surface tension (gamma(min)) of surfactant after antigen challenge was significantly increased with a spectrum of responses that included dysfunction in 6 of 13 asthmatics. Antigen challenge significantly altered the partitioning of surfactant phospholipid measured as a decreased ratio of large surfactant aggregates (LA) to small surfactant aggregates (SA), LA/SA ratio. Phosphatidylglycerol (PG) was significantly reduced in the LA of the dysfunctional asthmatic BALs. There was a corresponding significant increase in the ratio of phosphatidylcholine to PG, which strongly correlated with both increased gamma(min) and decreased LA/SA. Altered surfactant phospholipid properties correlated with surfactant dysfunction as well or better than either increased eosinophils or protein. Secretory phospholipase activity, measured in vitro, increased after antigen challenge and may explain the decrease in surfactant PG. In summary, alteration of phospholipids, particularly depletion of PG, in the LA of surfactant may be an important mechanism in asthma-associated surfactant dysfunction.

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls

“…It has also been observed that children with asthma have higher levels of PC32:0 in sputum compared with control subjects [23]. In atopic asthma, experimental antigen exposure has been shown to induce a reduction in PG in large surfactant aggregates collected from BAL [24]. Leakage of plasma proteins seems to be important for inactivation of 610 620 630 640 650 660 670 680 690 700 710 720 730 740 750 760 770 780 790 800 810 820 830 840 850 860 m/z surfactant [19,21,25].…”

Specific roles of phosphatidylglycerols in hosts and microbes

“…Also, the possibility that phospholipid itself might participate has been less studied. However, some evidence indicate that surfactant is dysfunctional in asthma with diminished PG content, relative loss of PC as well as increasd lysophospholipids (57). It has been suggested that in antigenchallenged patients, secreted phospholipase A2 could participate in surfactant dysfunction, since sPLA2 exhibit preference for PGs over PCs.…”

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.…”