Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung.
Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a glycosylated, glycophosphatidylinositol-anchored protein expressed in epithelial cells of various primate tissues. It binds gram-negative bacteria and is overexpressed in human cancers. CEACAM6 is associated with lamellar bodies of cultured type II cells of human fetal lung and protects surfactant function in vitro. In this study, we characterized CEACAM6 expression in vivo in human lung. CEACAM6 was present in lung lavage of premature infants at birth and increased progressively in intubated infants with lung disease. Of surfactant-associated CEACAM6, ∼80% was the fully glycosylated, 90-kDa form that contains the glycophosphatidylinositol anchor, and the concentration (3.9% of phospholipid for adult lung) was comparable to that for surfactant proteins (SP)-A/B/C. We examined the affinity of CEACAM6 by purification of surfactant on density gradient centrifugation; concentrations of CEACAM6 and SP-B per phospholipid were unchanged, whereas levels of total protein and SP-A decreased by 60%. CEACAM6 mRNA content decreased progressively from upper trachea to peripheral fetal lung, whereas protein levels were similar in all regions of adult lung, suggesting proximal-to-distal developmental expression in lung epithelium. In adult lung, most type I cells and ∼50% of type II cells were immunopositive. We conclude that CEACAM6 is expressed by alveolar and airway epithelial cells of human lung and is secreted into lung-lining fluid, where fully glycosylated protein binds to surfactant. Production appears to be upregulated during neonatal lung disease, perhaps related to roles of CEACAM6 in surfactant function, cell proliferation, and innate immune defense.
Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.
Cheryl
C
Chapin
Nicole A
NA
Bailey
Linda W
LW
Gonzales
Jae-Woo
JW
Lee
Robert F
RF
Gonzalez
Philip L
PL
Ballard
D000328:Adult; D056809:Alveolar Epithelial Cells / Q000378:metabolism*; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014132:Trachea / Q000378:metabolism
D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger