Surfactant protein D reduces alveolar macrophage apoptosis in vivo.
Surfactant protein D (SP-D) is a molecule of the innate immune system that recognizes the patterns of surface carbohydrate on pathogens and targets them for phagocytosis and killing. SP-D-deficient mice show an increased number of macrophages in the alveolar space, excess surfactant phospholipid, overproduction of reactive oxygen species, and the development of emphysema. We report here that SP-D-deficient mice have a 5- to 10-fold increase in the number of apoptotic and necrotic alveolar macrophages, as defined by annexin V and propidium iodine staining, respectively. Intrapulmonary administration of a truncated 60-kDa fragment of human recombinant SP-D reduces the number of apoptotic and necrotic alveolar macrophages and partially corrects the lipid accumulation in SP-D-deficient mice. The same SP-D fragment binds preferentially to apoptotic and necrotic alveolar macrophages in vitro, suggesting that SP-D contributes to immune homeostasis in the lung by recognizing and promoting removal of necrotic and apoptotic cells.
Clark
Howard
H
Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford, United Kingdom. howard.clark@bioch.ox.ac.uk
Palaniyar
Nades
N
Strong
Peter
P
Edmondson
Jess
J
Hawgood
Samuel
S
Reid
Kenneth B M
KB
D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000818:Animals; D017304:Annexin A5 / Q000032:analysis / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D002469:Cell Separation; D002474:Cell-Free System / Q000737:chemistry; D002498:Centrifugation; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006023:Glycoproteins / Q000008:administration & dosage* / Q000032:analysis / Q000172:deficiency / Q000235:genetics; D006801:Humans; D020287:In Situ Nick-End Labeling; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000166:cytology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009336:Necrosis; D010446:Peptide Fragments / Q000008:administration & dosage; D010743:Phospholipids / Q000032:analysis; D011419:Propidium / Q000032:analysis / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000032:analysis / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D013194:Staining and Labeling
D017304:Annexin A5; D006023:Glycoproteins; D010446:Peptide Fragments; D010743:Phospholipids; D011506:Proteins; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D011419:Propidium; D016650:Fluorescein-5-isothiocyanate