Surfactant protein-D regulates the postnatal maturation of pulmonary surfactant lipid pool sizes.
Surfactant protein (SP)-D plays an important role in host defense and pulmonary surfactant homeostasis. In SP-D-deficient (Sftpd(-/-)) mice, the abnormal large surfactant forms seen at the ultrastructural level are taken up inefficiently by type II cells, resulting in an over threefold increase in the surfactant pool size. The mechanisms by which SP-D influences surfactant ultrastructure are unknown. We hypothesized that SP-D binds to surfactant immediately after being secreted and influences surfactant ultrastructure conversion. In newborn and adult sheep lungs, immunogold-labeled SP-D was associated with both lamellated membranous lipid structures of newly secreted surfactant and with small aggregate surfactant but not with tubular myelin. Since SP-D preferentially binds to phosphatidylinositol (PI) in vitro, the postnatal changes in PI were assessed. PI content in the bronchoalveolar lavage fluid increased after birth and peaked at 2-5 days of age, a time of rapid conversion of surfactant forms that is associated with the peak of surfactant lipid pool size. SP-D selectively interacted with PI-rich liposomes in vitro, causing their lysis. Similarly, the abnormal surfactant ultrastructure in Sftpd(-/-) mice was corrected by the addition of SP-D or melittin, and both peptides caused lysis of lipid vesicles. The normal conversion of surfactant ultrastructure requires SP-D that preferentially interacts with PI-rich, newly secreted surfactant, causing lysis of surfactant lipid membranes, converting the lipid forms into smaller surfactant lamellated structures that are critical for surfactant uptake by type II cells and normal surfactant homeostasis. SP-D regulates the dramatic decreases in the surfactant pool size that occurs in the newborn period.
Ikegami
Machiko
M
Div. of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, ML #7029, 3333 Burnet Ave., Cincinnati, Ohio 45229-3039, USA. machiko.ikegami@cchmc.org
Grant
Shawn
S
Korfhagen
Thomas
T
Scheule
Ronald K
RK
Whitsett
Jeffrey A
JA
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008555:Melitten / Q000378:metabolism / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010713:Phosphatidylcholines / Q000032:analysis / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011994:Recombinant Proteins; D012756:Sheep
D008563:Membrane Lipids; D010713:Phosphatidylcholines; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D008555:Melitten