Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D.
Surfactant protein D (SP-D) is an oligomeric C type lectin that promotes phagocytosis by binding to microbial surface carbohydrates. A 340-kDa glycoprotein (gp-340) has been shown to bind SP-D in the presence of calcium but does so independently of carbohydrate recognition. This protein exists both in a soluble form and in association with the membranes of alveolar macrophages. The primary structure of gp-340 has been established by molecular cloning, which yielded a 7,686-bp cDNA sequence encoding a polypeptide chain of 2, 413 amino acids. The domain organization features 13 scavenger receptor cysteine-rich (SRCR) domains, each separated by an SRCR-interspersed domain, except for SRCRs 4 and 5, which are contiguous. The 13 SRCR domains are followed by two C1r/C1s Uegf Bmp1 domains separated by a 14th SRCR domain and a zona pellucida domain. gp-340 seems to be an alternative spliced form of DMBT1. Reverse transcription-PCR analysis showed that the main sites of synthesis of gp-340 are lung, trachea, salivary gland, small intestine, and stomach. Immunohistochemistry revealed strong staining for gp-340 in alveolar and other tissue macrophages. Immunostaining of the macrophage membrane was either uniform or focal in a way that suggested capping, whereas other macrophages showed strong intracellular staining within the phagosome/phagolysosome compartments. In some macrophages, SP-D and gp-340 were located in the same cellular compartment. Immunoreactive gp-340 was also found in epithelial cells of the small intestine and in the ducts of salivary glands. The distribution of gp-340 in macrophages is compatible with a role as an opsonin receptor for SP-D.
Holmskov
U
U
Department of Immunology and Microbiology, Institute of Medical Biology, University of Southern Denmark, Winslowparken 19.1, DK-5000 Odense, Denmark. holmskov@imbmed.sku.dk
Mollenhauer
J
J
Madsen
J
J
Vitved
L
L
Gronlund
J
J
Tornoe
I
I
Kliem
A
A
Reid
K B
KB
Poustka
A
A
Skjodt
K
K
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000378:metabolism; D009895:Opsonin Proteins / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018987:Salivary Ducts / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D006023:Glycoproteins; D009895:Opsonin Proteins; D011510:Proteolipids; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011971:Receptors, Immunologic; C116303:glycoprotein 340