Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement

Kimura, Yuko; Miwa, Takashi; Zhou, Lin; Song, Wen‐Chao

doi:10.1182/blood-2007-05-089821

Cited by 114 publications

(144 citation statements)

References 34 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…However, additional evidence has demonstrated that properdin could promote de novo C3 convertase assembly when immobilized to an inert surface and initiate C3 convertase formation on microbial surfaces (such as Neisseria gonorrhoeae) [31,32]. The novel role of properdin in AP complement initiation was supported by evidence from a properdin knockout mouse model [33]. Additionally, it has been reported that C3 and C5 can be directly cleaved by proteases unrelated to the complement cascade, such as kallikrein and thrombin (which are involved in coagulation), leading to an additional source of anaphylatoxins (C5a and C3a) and establishing a novel and potentially important connection between the complement and coagulation cascades [34,35].…”

Section: Classicalmentioning

confidence: 69%

Complement and its role in innate and adaptive immune responses

2009

Self Cite

View full text Add to dashboard Cite

The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.

show abstract

Section: Classicalmentioning

confidence: 69%

Complement and its role in innate and adaptive immune responses

2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…direct recognition by properdin for AP complement activation. Reported patterns include exogenous microorganisms (7,24), endogenous cells (25)(26)(27), and various biological substrates (9,28,29); however, many of these experiments were performed in systems permitting either C3 activation with initial C3b deposition or in buffer systems with purified properdin. In the presence of intact C3, it is virtually impossible to demonstrate whether properdin acts in a recognition manner or subsequently binds to C3b.…”

Section: Significancementioning

confidence: 99%

“…These claims were controversial, and properdin-dependent complement activation was dismissed by the scientific community (2-4); however, the "properdin system" was reborn as the alternative pathway (AP) more than 20 y later (3), with properdin described as a stabilizer and positive regulator of the AP C3 convertase (5,6). Properdin and its possible different roles in complement activation have been a basis for further studies in this area (7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Properdin binding to complement activating surfaces depends on initial C3b deposition

Harboe

Johnson

Nymo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Two functions have been assigned to properdin; stabilization of the alternative convertase, C3bBb, is well accepted, whereas the role of properdin as pattern recognition molecule is controversial. The presence of nonphysiological aggregates in purified properdin preparations and experimental models that do not allow discrimination between the initial binding of properdin and binding secondary to C3b deposition is a critical factor contributing to this controversy. In previous work, by inhibiting C3, we showed that properdin binding to zymosan and Escherichia coli is not a primary event, but rather is solely dependent on initial C3 deposition. In the present study, we found that properdin in human serum bound dose-dependently to solid-phase myeloperoxidase. This binding was dependent on C3 activation, as demonstrated by the lack of binding in human serum with the C3-inhibitor compstatin Cp40, in C3-depleted human serum, or when purified properdin is applied in buffer. Similarly, binding of properdin to the surface of human umbilical vein endothelial cells or Neisseria meningitidis after incubation with human serum was completely C3-dependent, as detected by flow cytometry. Properdin, which lacks the structural homology shared by other complement pattern recognition molecules and has its major function in stabilizing the C3bBb convertase, was found to bind both exogenous and endogenous molecular patterns in a completely C3-dependent manner. We therefore challenge the view of properdin as a pattern recognition molecule, and argue that the experimental conditions used to test this hypothesis should be carefully considered, with emphasis on controlling initial C3 activation under physiological conditions.

show abstract

“…, Figure 6a. Interestingly, type C particles were able to increase alternative pathway turnover through interaction with properdin (a positive regulator as well as a recently identified initiator of alternative pathway) 34,35 as demonstrated in reduction of Bb levels in the presence of antiproperdin antibodies (Figure 6b). This is presumably due to noncovalent binding of properdin to poloxamine chains, thereby recruiting C3b and allowing for alternative pathway convertase build-up.…”

mentioning

confidence: 99%

Distinct Polymer Architecture Mediates Switching of Complement Activation Pathways at the Nanosphere−Serum Interface: Implications for Stealth Nanoparticle Engineering

et al. 2010

View full text Add to dashboard Cite

Nanoparticles with surface projected polyethyleneoxide (PEO) chains in "mushroom؊brush" and "brush" configurations display stealth properties in systemic circulation and have numerous applications in sitespecific targeting for controlled drug delivery and release as well as diagnostic imaging. We report on the "structure؊activity" relationship pertaining to surface-immobilized PEO of various configurations on model nanoparticles, and the initiation of complement cascade, which is the most ancient component of innate human immunity, and its activation may induce clinically significant adverse reactions in some individuals. Conformational states of surface-projected PEO chains, arising from the block copolymer poloxamine 908 adsorption, on polystyrene nanoparticles trigger complement activation differently. Alteration of copolymer architecture on nanospheres from mushroom to brush configuration not only switches complement activation from C1q-dependent classical to lectin pathway but also reduces the level of generated complement activation products C4d, Bb, C5a, and SC5b-9. Also, changes in adsorbed polymer configuration trigger alternative pathway activation differently and through different initiators. Notably, the role for properdin-mediated activation of alternative pathway was only restricted to particles displaying PEO chains in a transition mushroom؊brush configuration. Since nanoparticle-mediated complement activation is of clinical concern, our findings provide a rational basis for improved surface engineering and design of immunologically safer stealth and targetable nanosystems with polymers for use in clinical medicine.

show abstract

Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement

Cited by 114 publications

References 34 publications

Complement and its role in innate and adaptive immune responses

Complement and its role in innate and adaptive immune responses

Properdin binding to complement activating surfaces depends on initial C3b deposition

Distinct Polymer Architecture Mediates Switching of Complement Activation Pathways at the Nanosphere−Serum Interface: Implications for Stealth Nanoparticle Engineering

Contact Info

Product

Resources

About