Disease relevance of Mbl2

• Results of the passive hemolysis experiment using sheep erythrocytes coated with yeast mannan suggest that this MBP has the ability to activate complement [1].
• The objective of this study is to investigate the involvement of MBP in IgA nephropathy by using HIGA mice, which spontaneously develop a glomerulonephritis resembling human IgA nephropathy [2].
• We have found that MBP recognizes and binds specifically to oligosaccharide ligands expressed on the surfaces of a human colorectal carcinoma [3].
• Taken together, the data show that MBL modulates the response to HSV-2 in mice by affecting neutralization of the virus [4].
• CONCLUSIONS: These results indicate that neither MBL nor activation of the complement cascade is crucial for the induction of anaphylaxis [5].

High impact information on Mbl2

• Our study provides direct evidence that MBL plays a key role in restricting the complications associated with S. aureus infection in mice and raises the idea that the MBL gene may act as a disease susceptibility gene against staphylococci infections in humans [6].
• Furthermore, we demonstrated that neutrophils and MBL are required to limit intraperitoneal infection with S. aureus [6].
• Mannan-binding protein (MBP), a Ca2+-dependent mammalian lectin specific for mannose and N-acetylglucosamine, is an important serum component associated with innate immunity [3].
• Interestingly, the recombinant vaccinia virus carrying human MBP gene was demonstrated to possess a potent growth-inhibiting activity against human colorectal carcinoma cells transplanted in KSN nude mice when administered by intratumoral or subcutaneous injection [3].
• Mannose-binding lectin (MBL) and ficolins are pattern recognition proteins acting in innate immunity, and they trigger the activation of the lectin complement pathway through MBL-associated serine proteases (MASPs) [7].

Chemical compound and disease context of Mbl2

• Finally, parenteral administration of MBL increased resistance of mice to hematogenously disseminated candidiasis [8].

Biological context of Mbl2

• Mouse Mbl1 and Mbl2 have five and six exons, respectively [9].
• These findings suggest that L-MBP plays a role in mucosal innate immunity [10].
• This suggests that lack of MBL-mediated complement activation increases susceptibility to viral infection [4].
• RESULTS: After antigenic challenge a marked drop in body temperature as well as a rapid decrease in serum MBL levels were observed [5].
• Thus, MBL-mediated protection was limited to the effects of preservation of liver homeostasis [4].

Anatomical context of Mbl2

• L-MBP is expressed in epithelial cells of mouse small intestine [10].
• Immunohistochemical staining with an mAb against mouse L-MBP and in situ hybridization revealed that L-MBP is selectively expressed in some villous epithelial cells of the small intestine [10].
• In addition to liver, S-MBP mRNA was detected in lung, kidney, and testis, and L-MBP mRNA was detected in kidney, thymus, and small intestine [10].
• In contrast mast cell activation is associated with the development of hypothermia and possibly the observed decrease in serum MBL levels [5].
• Ligands on surfaces of endothelial cells that are exposed due to the ischaemia may be recognized by pattern recognition molecules such as mannan-binding lectin (MBL), inducing complement activation [11].

Associations of Mbl2 with chemical compounds

• Characterization of murine mannose-binding protein genes Mbl1 and Mbl2 reveals features common to other collectin genes [9].
• Western blotting with polyclonal Abs against rat L-MBP demonstrated this protein in Triton X-100 extracts of the small intestine obtained from mice that had undergone systemic perfusion [10].
• Deposition of mannan-binding protein in glomeruli of HIGA mice in the exacerbation of glomerulonephrites induced by lipopolysaccharide [2].
• Lung injury in mice after GI/R is MBL and C1q independent, but C2 dependent, suggesting a potential role for ficolins in this model [12].
• The binding of mouse MBP to mannan could be inhibited by mono- and disaccharides in the following order of potency: L-fucose > D-mannose > N-acetyl-D-glucosamine > maltose > D-mannoheptulose > D-glucose > N-acetyl-D-mannosamine >> lactose > D-galactose >> N-acetyl-D-galactosamine [13].

Other interactions of Mbl2

• The results implicate SP-D and possibly MBL as important components of the innate defense of the respiratory tract against influenza virus and indicate that the degree or pattern of glycosylation of a virus can be an important factor in its virulence [14].
• These results confirm an essential function for complement in host resistance against S. aureus infection but also identify an MBL-dependent mechanism that is C3 independent [15].

Analytical, diagnostic and therapeutic context of Mbl2

• Quantitative RT-PCR revealed that the small intestine is a predominant site of extrahepatic expression of L-MBP [10].
• The mannan-binding protein fraction of bovine serum that eluted with 100 mM mannose from a mannan-Sepharose column was analyzed under reducing conditions by SDS-PAGE [1].
• The concentration of MBP in serum from normal mice was measured by rocket immunoelectrophoresis and found to be from below 1 microgram/ml to 100 micrograms/ml (average 50 micrograms/ml, n = 60) [13].
• Kidney damages, which were evaluated by levels of blood urea nitrogen (BUN) and creatinine, showed that MBL DKO mice were significantly protected compared with WT mice [11].
• Mice subjected to renal I/R displayed evident renal MBL-depositions, depending on the duration of warm ischemia, in the early reperfusion phase [16].

References