Human mannose-binding protein activates the alternative complement pathway and enhances serum bactericidal activity on a mannose-rich isolate of Salmonella.

Schweinle, Jo Ellen; Ezekowitz, R. A. B.; Tenner, Andrea J.; Kuhlman, M.; Joiner, Keith A.

doi:10.1172/jci114367

Cited by 132 publications

(68 citation statements)

References 46 publications

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“…MBL (formerly called MBP; first isolated by Kawasaki et al 28 ) has been shown to bind to the LPSs of Salmonella and Klebsiella O3, which have an O-region rich in D-mannose. 29,30 In addition, Kawakami and his coworkers found a complement-dependent bactericidal factor in nonimmune mouse sera. [31][32][33] Having found that this factor binds to the Ra core region of Salmonella LPS, they decided to call it "Ra-reactive factor" (RaRF).…”

Section: Involvement Of the Lectin Pathway In The Platelet Response Tmentioning

confidence: 99%

LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system

Zhao

Ohtaki

Yamaguchi

et al. 2002

Blood

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Section: Involvement Of the Lectin Pathway In The Platelet Response Tmentioning

confidence: 99%

LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system

Zhao

Ohtaki

Yamaguchi

et al. 2002

Blood

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“…Salmonella CO differs from BO and DO by its reactivity with MBL [16]. MBL recognises carbohydrate structures such as Nacetylglucosamine and mannose, and is thought to recruit C3 through the activation of the classical pathway C3 convertase, C4bC2a, by the MBL/MASP1/MASP2 complex [17,18].…”

Section: C2 Deficiency and Igm/igg Switching 557mentioning

confidence: 99%

“…Salmonella serogroup C was later shown to react with mannan-binding lectin (MBL) [16], the recognition protein of the MBL pathway of complement [17]. According to current concepts, this activation mechanism involves the recruitment of classical pathway C3 convertase, C4bC2a, by complexes containing MBL and the MBL-associated serine proteases MASP-1 and MASP-2 [17,18].…”

Section: Introductionmentioning

confidence: 99%

Low Concentrations of Immunoglobulin G Antibodies to Salmonella Serogroup C in C2 Deficiency: Suggestion of a Mannan‐Binding Lectin Pathway‐Dependent Mechanism

et al. 1999

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The influence of complement on immune responses to polysaccharides is debatable. We examined the serum concentrations of IgM and IgG antibody against Salmonella O-antigen specific oligosaccharides representing the serogroups B, C and D, and against capsular polysaccharides of Streptococcus pneumoniae serotypes 6 and 23 in C2-deficient adults and in healthy controls. A sharp contrast of findings was found for antibodies against the CO antigen, an activator of the mannan-binding lectin (MBL) pathway of complement activation. The C2-deficient group showed normal IgM and markedly low IgG antibody levels. Similar findings were made in adults with low concentrations of MBL. This suggests that the recruitment of classical pathway C3 convertase through the MBL pathway is critically involved in isotype switching of antibodies against MBL pathway activating antigens during immune system maturation. The findings imply a new role of the MBL pathway, and an additional link between innate and acquired immunity. Specific IgM against BO was moderately low in C2 deficiency. Other differences for the Salmonella antigens were not found. Markedly raised IgM antibody levels against pneumococcal polysaccharides in C2 deficiency probably Salmonella reflected past infections. The absence of a concomitant increase of specific IgG might possibly be explained by impaired IgM to IgG switching.

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“…MBL promotes phagocytosis and complement-mediated killing of bacteria (S. montevideo [12,21], S. typhimurium [13] and Escherichia coli [14]) and yeast (Candida albicans [11]). Complement is also activated when MBL binds to gp 120 of human immunodeficiency virus (HIV)-1 and gp 110 of HIV-2 [22], and MBL has been reported to inhibit HIV-1 infection of H9 lymphoblasts [18].…”

Section: Introductionmentioning

confidence: 99%

Reconstitution of Opsonizing Activity by Infusion of Mannan‐Binding Lectin (MBL) to MBL‐Deficient Humans

Valdimarsson¹,

et al. 1998

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Reconstitution ofOpsonizing Activity by Infusion of Mannan-Binding Lectin (MBL) to MBL-Deficient Humans. Scand J Immunol 1998;48:116-123 Mannan-binding lectin (MBL, previously named mannan-binding protein, MBP) is a serum collectin, which activates complement upon binding to microbial carbohydrates. This results in opsonization of the microorganisms as well as direct complement-mediated killing. Clinical evidence indicates that MBL has an important role in the innate immune defence against various pathogens. Genetically determined MBL deficiency is associated with increased susceptibility to infections. We have infused two MBL-deficient individuals with clinical grade MBL, purified from pooled donor plasma, in doses sufficient to attain normal concentration of MBL in serum. This resulted in normalization of complement-mediated opsonization. An initial rapid decrease in the serum concentration of MBL was followed by a slower decline with an estimated half-life of about 6 days. No adverse effects were observed and anti-MBL antibodies could not be detected following several MBL infusions. One of the two MBL recipient, a two-year-old girl, who had been suffering from repeated infections from the age of 4 months, was given a total of six MBL infusions. She has subsequently remained healthy for more than three years.

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Human mannose-binding protein activates the alternative complement pathway and enhances serum bactericidal activity on a mannose-rich isolate of Salmonella.

Cited by 132 publications

References 46 publications

LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system

LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system

Low Concentrations of Immunoglobulin G Antibodies to Salmonella Serogroup C in C2 Deficiency: Suggestion of a Mannan‐Binding Lectin Pathway‐Dependent Mechanism

Reconstitution of Opsonizing Activity by Infusion of Mannan‐Binding Lectin (MBL) to MBL‐Deficient Humans

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