Adsorption of surfactant to bronchial epithelium: possible role of receptor 'unmasking' in asthma.
BACKGROUND
In a recent study in animals it has been shown how surface-active phospholipid (SAPL) in the form of a commercially available micronized (5 micromphi) dry powder (ALECT/PumactantT) was able to reduce afferent neural feedback to the brainstem in response to a methacholine challenge by the same order of magnitude as drugs commonly prescribed for asthma. The underlying theory assumed that adsorption of SAPL to bronchial epithelium masked irritant receptors eliciting the bronchoconstrictor reflex, thus providing a barrier to noxious stimuli entering the lungs.


OBJECTIVE
To test the underlying assumption that SAPL was actually adsorbed (i.e., bound to bronchial epithelium), especially the major and most surface-active component of lung surfactant, namely dipalmitoyl phosphatidylcholine (DPPC). A secondary objective was to investigate any role of phosphatidylglycerol (PG) in promoting the adsorption of DPPC.


METHODS
Radiolabeled DPPC dispersed ultrasonically in saline was used to incubate excised sections of porcine bronchial epithelium. The adsorbed DPPC was then quantified by rigorously rinsing the tissue of adhering fluid and then digesting it for beta-scintillation counting. Each test (n=8 runs) was repeated for ratios of DPPC:PG of 9:1, 7:3 (as per ALECT/PumactantT) and 1:1 for both dipalmitoyl PG (DPPG) and EggPG (as incorporated in ALECT/PumactantT).


RESULTS
Despite rigorous rinsing postincubation, bronchial epithelium was found to adsorb DPPC at a level roughly equivalent to one close-packed monolayer; whereas both DPPG and EggPG promoted the adsorption of DPPC in a dose-dependent manner, reaching an approximate threefold increase for 7:3 DPPC:PG.


CONCLUSIONS
DPPC adsorbs to bronchial epithelium in amounts necessary for the masking of receptors, and this adsorption (probably chemisorption) is quite strongly promoted by PG either in its indigenous state (DPPG) or in the form (EggPG) used in ALECT to suppress the sensitivity of bronchial irritant receptors in our previous study and in clinical trials just completed.
Hills
B A
BA
Pediatric Respiratory Research Centre, Mater Children's Hospital, South Brisbane, Queensland, Australia. bhills@mmri.mater.org.au
Chen
Y
Y
Hills
Y C
YC
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000493:pharmacokinetics*; D000818:Animals; D001980:Bronchi; D066298:In Vitro Techniques; D023421:Models, Animal; D010715:Phosphatidylglycerols / Q000493:pharmacokinetics*; D011663:Pulmonary Surfactants / Q000493:pharmacokinetics*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*; D013552:Swine
D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; D011956:Receptors, Cell Surface; D015060:1,2-Dipalmitoylphosphatidylcholine