Human lung surfactant protein A exists in several different oligomeric states: oligomer size distribution varies between patient groups.
BACKGROUND
Lung surfactant protein A (SP-A) is a complex molecule composed of up to 18 polypeptide chains. In vivo, SP-A probably binds to a wide range of inhaled materials via the interaction of surface carbohydrates with the lectin domains of SP-A and mediates their interaction with cells as part of a natural defense system. Multiplicity of lectin domains gives high-affinity binding to carbohydrate-bearing surfaces.


METHODS
Gel filtration analyses were performed on bronchoalveolar lavage (BAL) fluid samples from three patient groups: pulmonary alveolar proteinosis (n = 12), birch pollen allergy (n = 11), and healthy volunteers (n = 4). Sucrose density gradient centrifugation was employed to determine molecular weights of SP-A oligomers. SP-A was solubilized from the lipid phase to compare oligomeric state with that of water soluble SP-A.


RESULTS
SP-A exists as fully assembled complexes with 18 polypeptide chains, but it is also consistently found in smaller oligomeric forms. This is true for both the water- and lipid-soluble fractions of SP-A.


CONCLUSIONS
The three patient groups analyzed show a shift towards lower oligomeric forms of SP-A in the following sequence: healthy-pulmonary alveolar proteinosis-pollen allergy. Depolymerization would be expected to lead to loss of binding affinity for carbohydrate-rich surfaces, with loss or alteration of biological function. While there are many complex factors involved in the establishment of an allergy, it is possible that reduced participation of SP-A in clearing a potential allergen from the lungs could be an early step in the chain of events.
Hickling
T P
TP
Department of Biochemistry, University of Oxford, U.K.
Malhotra
R
R
Sim
R B
RB
D000485:Allergens; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008970:Molecular Weight; D011058:Pollen; D011487:Protein Conformation; D011510:Proteolipids / Q000737:chemistry* / Q000302:isolation & purification; D011649:Pulmonary Alveolar Proteinosis / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000302:isolation & purification; D012130:Respiratory Hypersensitivity / Q000378:metabolism*
D000485:Allergens; D008055:Lipids; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants