Mannan-binding protein (MBP) is Mannan-binding protein (MBP),1 also called mannose-binding protein (MBP) or mannan-binding lectin, is a Ca 2ϩ -dependent (C-type) serum lectin and an important serum component associated with innate immunity (1-4). Human MBP is a homo-oligomer of an ϳ31-kDa subunit, each subunit containing a carbohydrate recognition domain followed by a short neck region on the COOH-terminal side and a collagen-like domain followed by a short cysteine-rich region on the NH 2 -terminal side. Three subunits form a structural unit, and MBP normally consists of two to six structural units joined through disulfide bonds at the amino termini, the whole molecular mass being ϳ200 -600 kDa (5, 6).The carbohydrate specificity of MBP is rather broad (it binds to mannose, N-acetylglucosamine, and fucose) in accordance with the fact that MBP binds to the cell surfaces of a wide variety of pathogens (7,8). MBP exhibits complement-dependent bactericidal activity, i.e. the Escherichia coli K12 and B strains, which have exposed N-acetylglucosamine and L-glycero-D-mannoheptose residues, respectively, are killed by MBP with the aid of complement (8). In addition, 1-deoxymannojirimycin (an ␣-mannosidase inhibitor)-treated baby hamster kidney cells, which have high mannose type oligosaccharides exposed on their surfaces, are also killed by MBP with the aid of complement (9). This complement activation pathway is called the lectin pathway (10). MBP has also been shown to function as a direct opsonin (11) and to prevent virus infection (12, 13). 1 The abbreviations used are: MBP, mannan-binding protein; AAL, A. aurantia lectin; CID, collision-induced dissociation; ConA, concanavalin A; FACS, fluorescence-activated cell sorter; FCS, fetal calf serum; FITC, fluorescein 4-isothiocyanate; Fuc, fucose; Hex, hexose; HexNAc, N-acetylhexosamine; HPLC, high performance liquid chromatography; LA, lectin affinity; LacNAc, N-acetyllactosamine; LCA, Lens culinaris lectin; Le, Lewis antigen; LTA, Lotus tetragonolobus lectin; mAb, monoclonal antibody; MALDI, matrix-assisted laser desorption/ ionization; MLO, MBP ligand oligosaccharides; MLO-A1, MBP ligand oligosaccharide-acidic fraction (monosialylated); MLO-N, MBP ligand oligosaccharide-neutral fraction; MS, mass spectrometry; MS/MS, tandem mass spectrometry; nano-ESI, nanoelectrospray ionization; PA, 2-aminopyridine; PBS, phosphate-buffered saline; PHA-E4, P. vulgaris erythroagglutinating lectin; PHA-L4, P. vulgaris leukoagglutinating lectin; PNA, peanut lectin; TOF, time-of-flight. All of the sugar residues have the D configuration except fucose, which has the L configuration.

The serum mannan-binding protein (MBP) is a host defense

-Increased prostaglandin production is implicated in the pathogenesis of glomerular disease. With this consideration, we examined the combined effects of reactive oxygen species and platelet-derived growth factor (PDGF), which might initiate glomerular dysfunction, on arachidonic acid release and cytosolic phospholipase A2 (cPLA2) activation in rat mesangial cells. H2O2-induced release of arachidonic acid was enhanced by PDGF, which by itself had little effect on the release, and the enhancement was completely inhibited by a cPLA2 inhibitor. The phosphorylation of cPLA2, extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein (MAP) kinase was upregulated by H2O2 or PDGF alone and except for ERK was enhanced further by the two in combination. The release of arachidonic acid induced by PDGF together with H2O2 was inhibited partially by an inhibitor of ERK or p38 MAP kinase and completely when the two inhibitors were combined; the inhibitory pattern was similar to that for the phosphorylation of cPLA2. These results suggest that the ERK and p38 MAP kinase pathways are involved in the increase in cPLA2 activation and arachidonic acid release induced by PDGF together with H2O2. hydrogen peroxide; p38 mitogen-activated protein kinase; extracellular signal-regulated kinase; cytosolic phospholipase A2; platelet-derived growth factor MESANGIAL CELLS SYNTHESIZE vasodilatory prostaglandins (PGs) such as PGE 2 , which act as relaxing factors and regulate glomerular hemodynamics under physiological conditions. However, an increase in renal PGE 2 production, which is observed in renal diseases such as glomerulonephritis and diabetic glomerulopathy, induces a functional disorder of the mesangium including abnormal glomerular filtration rate and is implicated in the pathogenesis of nephropathy (46,52).Previously, reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ), superoxide anion, and hydroxyl radical were recognized to cause cell injury and therefore be involved in the pathogenesis of various diseases. However, recent observations indicate that ROS cause physiological responses other than pathological responses, including protein phosphorylation, Ca 2ϩ signaling, and the activation of transcription factors by stimulating intracellular signaling systems, thus suggesting that ROS function as second messengers in the signal transduction pathway stimulated by the proinflammatory cytokines interleukin-1␤ and tumor necrosis factor-␣ (21,36,38,50).In glomerular disorders, ROS are generated by several inflammatory cells including neutrophils, monocytes, and macrophages gathered in the inflamed glomeruli, and also by the mesangial cell itself (7, 9, 10). Previous studies revealed that the intracellular generation of ROS or exposure to H 2

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