Glycoprotein-340 Binds Surfactant Protein-A (SP-A) and Stimulates Alveolar Macrophage Migration in an SP-A–Independent Manner

Abstract

Glycoprotein-340 (gp-340) was first identified as a surfactant protein (SP)-D-binding molecule purified from lung lavage of patients with alveolar proteinosis (Holmskov, et al., J. Biol. Chem. 1997;272:13743). In purifying SP-A from proteinosis lavage, we isolated a protein that copurifies with SP-A and SP-D and that was later found by protein sequencing to be gp-340. We have shown that soluble gp-340 binds SP-A in a calcium-dependent manner independent of the lectin activity of SP-A. To examine the functional significance of this interaction, we tested the ability of soluble gp-340 to block SP-A binding to and stimulation of the chemotaxis of alveolar macrophages. We found that gp-340 does not affect the binding of SP-A to alveolar macrophages over a wide range of SP-A concentrations, nor does it inhibit the ability of SP-A to stimulate macrophage chemotaxis. We also found that gp-340 alone stimulates the random migration (chemokinesis) of alveolar macrophages in a manner independent of SP-A-stimulated chemotaxis. These results suggest that gp-340 is not a cell-surface receptor necessary for SP-A stimulation of chemotaxis, and show that gp-340 can directly affect macrophage function.

Identification of the Bacteria-binding Peptide Domain on Salivary Agglutinin (gp-340/DMBT1), a Member of the Scavenger Receptor Cysteine-rich Superfamily

“…SRCR proteins, e.g. the macrophage scavenger receptor, Mac-2-binding protein, CD5, CD6, WC1, Ebnerin, CRP (cyclic AMP receptor protein)-ductin, and lung gp-340, are associated with host defense systems (7,8,(11)(12)(13)(14)(15)(16)(17). Until now, studies dealing with agglutinin-bacteria interactions have been focused mainly on the characterization of bacterial receptors (18,19) and identification of their cognate carbohydrate ligands on agglutinin (1, 20 -22).…”

Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

“…It has also been established that the binding of SP-D to gp-340 is a protein-protein interaction rather than a lectin-carbohydrate interaction. Recently, it was shown that gp-340 also may bind to SP-A (17). Protein sequencing showed that gp-340 was a member of the scavenger receptor cysteine-rich (SRCR) superfamily (16).…”

“…Recently, gp-340 also has been shown to bind SP-A in a calcium-dependent manner that is independent of the latter's lectin activity (17), but gp-340 neither affected the binding of SP-A to alveolar macrophages nor inhibited the ability of SP-A to stimulate macrophage chemotaxis. It was shown that gp-340 alone stimulates the random migration of alveolar macrophages in a manner independent of SP-A-stimulated chemotaxis.…”

Toll-like Receptor 2 (TLR2), Transforming Growth Factor-β, Hyaluronan (HA), and Receptor for HA-mediated Motility (RHAMM) Are Required for Surfactant Protein A-stimulated Macrophage Chemotaxis

“…Additionally, the scavenger protein glycoprotein-340 binds SPA in a carbohydrate recognition domain-independent manner, but it does not affect binding of SPA to alveolar macrophages or SPA stimulation of macrophage chemotaxis. However, glycoprotein-340 directly stimulates random migration (chemokinesis) of alveolar macrophages (48). SPA can also bind to CD14, a known pattern recognition co-receptor for LPS and PGN, that mediates release of pro-inflammatory cytokines (49).…”