HUMAN COMPLEMENT ACTIVATION VIA THE ALTERNATIVE PATHWAY ON PORCINE ENDOTHELIUM INITIATED BY IgA ANTIBODIES

Af, Schaapherder; Gooszen, H. G.; Bulte, te; Mr, Daha

doi:10.1097/00007890-199508000-00014

Cited by 47 publications

(22 citation statements)

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“…It is generally agreed that IgA cannot activate the classical complement pathway (14). Activation of the alternative complement pathway by IgA is supported by both in vitro (27)(28)(29) and in vivo observations (30), as well as by the present study. It has been argued that complement activation by IgA has to rely on studies using artificially modified or presented IgA (14).…”

Section: Discussionsupporting

confidence: 86%

“…However, complement activation has also been demonstrated upon binding of IgA to its natural Ag. For example, xenoreactive human IgA Abs can induce complement-mediated lysis of pig endothelial cells in a calcium-independent way (28). Furthermore, binding of human serum IgA to Streptococcus pneumonia induces neutrophil-mediated bacterial killing that was complement dependent and proceeded in the presence of MgEGTA (29).…”

Section: Discussionmentioning

confidence: 99%

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Human IgA Activates the Complement System Via the Mannan-Binding Lectin Pathway

Roos

et al. 2001

The Journal of Immunology

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386

286

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The recently identified lectin pathway of the complement system, initiated by binding of mannan-binding lectin (MBL) to its ligands, is a key component of innate immunity. MBL-deficient individuals show an increased susceptibility for infections, especially of the mucosal system. We examined whether IgA, an important mediator of mucosal immunity, activates the complement system via the lectin pathway. Our results indicate a dose-dependent binding of MBL to polymeric, but not monomeric IgA coated in microtiter plates. This interaction involves the carbohydrate recognition domain of MBL, because it was calcium dependent and inhibited by mannose and by mAb against this domain of MBL. Binding of MBL to IgA induces complement activation, as demonstrated by a dose-dependent deposition of C4 and C3 upon addition of a complement source. The MBL concentrations required for IgA-induced C4 and C3 activation are well below the normal MBL plasma concentrations. In line with these experiments, serum from individuals having mutations in the MBL gene showed significantly less activation of C4 by IgA and mannan than serum from wild-type individuals. We conclude that MBL binding to IgA results in complement activation, which is proposed to lead to a synergistic action of MBL and IgA in antimicrobial defense. Furthermore, our results may explain glomerular complement deposition in IgA nephropathy.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Human IgA Activates the Complement System Via the Mannan-Binding Lectin Pathway

Roos

et al. 2001

The Journal of Immunology

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386

286

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“…This complement activation is in agreement with previous observations on complement-mediated effects of IgA in other model systems (43)(44)(45). However, we also found that mIgA can significantly mediate complementdependent killing of S. pneumoniae, albeit at a much higher IgA concentration than is required by the polymeric form.…”

Section: Figuresupporting

confidence: 93%

Killing of Streptococcus pneumoniae by capsular polysaccharide–specific polymeric IgA, complement, and phagocytes

Janoff¹,

Fasching²,

Orenstein³

et al. 1999

J. Clin. Invest.

131

129

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The role of IgA in the control of invasive mucosal pathogens such as Streptococcus pneumoniae is poorly understood. We demonstrate that human pneumococcal capsular polysaccharide-specific IgA initiated dose-dependent killing of S. pneumoniae with complement and phagocytes. The majority of specific IgA in serum was of the polymeric form (pIgA), and the efficiency of pIgA-initiated killing exceeded that of monomeric IgA-initiated killing. In the absence of complement, specific IgA induced minimal bacterial adherence, uptake, and killing. Killing of S. pneumoniae by resting phagocytes with immune IgA required complement, predominantly via the C2-independent alternative pathway, which requires factor B, but not calcium. Both S. pneumoniae-bound IgA and complement were involved, as demonstrated by a 50% decrease in killing with blocking of Fcα receptor (CD89) and CR1/CR3 (CD35/CD11b). However, IgA-mediated killing by phagocytes could be reproduced in the absence of opsonic complement by pre-activating phagocytes with the inflammatory products C5a and TNF-α. Thus, S. pneumoniae capsule-specific IgA may show distinct roles in effecting clearance of S. pneumoniae in the presence or absence of inflammation. These data suggest mechanisms whereby pIgA may serve to control pneumococcal infections locally and upon the pathogen's entry into the bloodstream.

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“…For instance, they may be induced by contact between mucosal immune cells and intestinal flora 68 or food-derived antigens with epitopes similar to GAL. 69 Whether IgG, with a higher affinity for pig antigens, or IgM, which is supposed to act as an "early" antibody, plays the predominant role in complement activation and cytotoxicity has yet to be established. 70 In a recent study by Schraa et al, 71 rats were sensitized against hamsters 1 and 5 weeks before hepatic xenografting; high titers of IgM and IgG, respectively, were found.…”

Section: Humoral Responsementioning

confidence: 99%

“…As for the direct effect of complement, both the classical and the alternative pathways seem to be involved in the activation and cytotoxicity of a xenogeneic reaction. 69 …”

Section: Humoral Responsementioning

confidence: 99%

Extracorporeal Perfusion for the Treatment of Acute Liver Failure

et al. 2000

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Objective and Summary Background DataBecause of the shortage of available donor organs, death rates from liver failure remain high. Therefore, several temporary liver-assisting therapies have been developed. This article reviews various approaches to temporary liver support as well as immunologic and metabolic developments toward a solution for this problem. MethodsA literature review was performed using Medline and additional library searches to obtain further references. Only articles with a well-defined aim of study and methodology and a clear description of the outcome of the experiments were included. ConclusionsRenewed interest has developed in old and new methods for an extracorporeal approach to the treatment of acute liver failure. Although temporary clinical improvement has been established, further research is needed to achieve a successful long-term clinical outcome. New developments in the field of genetic modification and tissue engineering await clinical application in the near future.

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HUMAN COMPLEMENT ACTIVATION VIA THE ALTERNATIVE PATHWAY ON PORCINE ENDOTHELIUM INITIATED BY IgA ANTIBODIES

Cited by 47 publications

References 0 publications

Human IgA Activates the Complement System Via the Mannan-Binding Lectin Pathway

Human IgA Activates the Complement System Via the Mannan-Binding Lectin Pathway

Killing of Streptococcus pneumoniae by capsular polysaccharide–specific polymeric IgA, complement, and phagocytes

Extracorporeal Perfusion for the Treatment of Acute Liver Failure

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