title: Unexpected expression pattern for glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GPIHBP1) in mouse tissues revealed by positron emission tomography scanning.
abstract: Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), a GPI-anchored endothelial cell protein, binds lipoprotein lipase (LPL) and transports it into the lumen of capillaries where it hydrolyzes triglycerides in lipoproteins. GPIHBP1 is assumed to be expressed mainly within the heart, skeletal muscle, and adipose tissue, the sites where most lipolysis occurs, but the tissue pattern of GPIHBP1 expression has never been evaluated systematically. Because GPIHBP1 is found on the luminal face of capillaries, we predicted that it would be possible to define GPIHBP1 expression patterns with radiolabeled GPIHBP1-specific antibodies and positron emission tomography (PET) scanning. In Gpihbp1(-/-) mice, GPIHBP1-specific antibodies were cleared slowly from the blood, and PET imaging showed retention of the antibodies in the blood pools (heart and great vessels). In Gpihbp1(+/+) mice, the antibodies were cleared extremely rapidly from the blood and, to our surprise, were taken up mainly by lung and liver. Immunofluorescence microscopy confirmed the presence of GPIHBP1 in the capillary endothelium of both lung and liver. In most tissues with high levels of Gpihbp1 expression, Lpl expression was also high, but the lung was an exception (very high Gpihbp1 expression and extremely low Lpl expression). Despite low Lpl transcript levels, however, LPL protein was readily detectable in the lung, suggesting that some of that LPL originates elsewhere and then is captured by GPIHBP1 in the lung. In support of this concept, lung LPL levels were significantly lower in Gpihbp1(-/-) mice than in Gpihbp1(+/+) mice. In addition, Lpl(-/-) mice expressing human LPL exclusively in muscle contained high levels of human LPL in the lung.
authors.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute, Los Angeles, California 90095, USA.
authors.forename: Tove
authors.initials: T
authors.lastname: Olafsen
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.forename: Brandon S J
authors.initials: BS
authors.lastname: Davies
authors.forename: Anne P
authors.initials: AP
authors.lastname: Beigneux
authors.forename: Vania E
authors.initials: VE
authors.lastname: Kenanova
authors.forename: Constance
authors.initials: C
authors.lastname: Voss
authors.forename: Glen
authors.initials: G
authors.lastname: Young
authors.forename: Koon-Pong
authors.initials: KP
authors.lastname: Wong
authors.forename: Richard H
authors.initials: RH
authors.lastname: Barnes
authors.forename: Yiping
authors.initials: Y
authors.lastname: Tu
authors.forename: Michael M
authors.initials: MM
authors.lastname: Weinstein
authors.forename: Chika
authors.initials: C
authors.lastname: Nobumori
authors.forename: Sung-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
authors.forename: André
authors.initials: A
authors.lastname: Bensadoun
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wu
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
mesh_terms: D000818:Animals; D001665:Binding Sites; D002196:Capillaries / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D005786:Gene Expression Regulation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods; D018110:Receptors, Lipoprotein / Q000737:chemistry*
chemical_list: C472779:GPI-HBP1 protein, mouse; D017261:Glycosylphosphatidylinositols; D018110:Receptors, Lipoprotein