Complement-regulatory biomaterial coatings: Activity and selectivity profile of the factor H-binding peptide 5C6

Bechtler, Clément; Koutsogiannaki, Sophia; Umnyakova, Ekaterina S.; Hamid, Amal; Gautam, Avneesh; Sarigiannis, Yiannis; Pouw, Richard B.; Lamers, Christina; Rabbani, Said; Schmidt, Christoph Q.; Lambris, John D.; Ricklin, Daniel

doi:10.1016/j.actbio.2022.10.055

Cited by 9 publications

(7 citation statements)

References 56 publications

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“…However, we found that factor H recruited onto the liposome surface was still active, that is, it assisted in the degradation of C3b to iC3b, suggesting that the N-terminal CCP1–4 domains are still available and not rigidly bound to the fHep-lipids. 24,25 Interestingly, factor H also bound to MeO-PEG-liposomes, which was unexpected because we did not observe strong binding in the QCM-D study. Presumably, the PEG density on the liposomes was different from that on the QCM sensor chip surface, which enabled factor H to interact with the PEG chains directly or be caught between PEG chains.…”

Section: Resultsmentioning

confidence: 72%

“…Factor H-related proteins can possibly interact with fHep-lipids because of their structural similarity to factor H; therefore, we must consider this when evaluating the regulatory effect of fHep-lipids on the complement system. 25…”

Section: Different Ratios Of Fhep-k8c-lipids : Meo-peg-lipidsmentioning

confidence: 99%

“…24 The C3b-binding sites within factor H are in CCP domains 1-4 and 19-20, with CCP1-4 having complementregulatory activity. 24,25 C4BP is a 540 kDa protein present in different forms in the plasma, with the main form consisting of one b-chain (46 kDa) and 7 a-chains (72 kDa) linked together by disulfide bonds and hydrophobic forces in a central core. [20][21][22]26 C4BP is present in human plasma at a concentration of approximately 225 mg mL À1 and is the main fluidphase regulator of the classical and lectin complement pathways.…”

Section: Introductionmentioning

confidence: 99%

“…19,29,30 Different factor H and C4BP recriuting-peptides have previously been used as a means to augment the hemocompatibility of various biomaterials. 25,[31][32][33] In the present study, the ability of fHep-lipids to bind factor H, C4BP, and AT was investigated in a model system with purified proteins using a quartz crystal microbalance with dissipation monitoring (QCM-D), which is often used for the analysis of molecular interactions. 34 The liposomes were then modified with fHep-lipids and characterized before being incubated in pure factor H to investigate whether surface-bound factor H could help cleave C3b to iC3b.…”

Section: Introductionmentioning

confidence: 99%

“…19,29,30 Different factor H and C4BP recriuting-peptides have previously been used as a means to augment the hemocompatibility of various biomaterials. 25,31–33…”

Section: Introductionmentioning

confidence: 99%

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Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro

Adler,

Fritsch,

Fromell

et al. 2023

J. Mater. Chem. B

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Section: Resultsmentioning

confidence: 72%

Section: Different Ratios Of Fhep-k8c-lipids : Meo-peg-lipidsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…19,29,30 Different factor H and C4BP recriuting-peptides have previously been used as a means to augment the hemocompatibility of various biomaterials. 25,31–33…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro

Adler,

Fritsch,

Fromell

et al. 2023

J. Mater. Chem. B

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The complement system: A key player in the host response to infections

Jayaraman,

Walachowski,

Bosmann

2024

Eur J Immunol

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Infections are one of the most significant healthcare and economic burdens across the world as underscored by the recent coronavirus pandemic. Moreover, with the increasing incidence of antimicrobial resistance, there is an urgent need to better understand host–pathogen interactions to design effective treatment strategies. The complement system is a key arsenal of the host defense response to pathogens and bridges both innate and adaptive immunity. However, in the contest between pathogens and host defense mechanisms, the host is not always victorious. Pathogens have evolved several approaches, including co‐opting the host complement regulators to evade complement‐mediated killing. Furthermore, deficiencies in the complement proteins, both genetic and therapeutic, can lead to an inefficient complement‐mediated pathogen eradication, rendering the host more susceptible to certain infections. On the other hand, overwhelming infection can provoke fulminant complement activation with uncontrolled inflammation and potentially fatal tissue and organ damage. This review presents an overview of critical aspects of the complement‐pathogen interactions during infection and discusses perspectives on designing therapies to mitigate complement dysfunction and limit tissue injury.

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Complement‐targeted therapeutics: Are we there yet, or just getting started?

Ricklin

2024

Eur J Immunol

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Therapeutic interventions in the complement system, a key immune‐inflammatory mediator and contributor to a broad range of clinical conditions, have long been considered important yet challenging or even unfeasible to achieve. Almost 20 years ago, a spark was lit demonstrating the clinical and commercial viability of complement‐targeted therapies. Since then, the field has experienced an impressive expansion of targeted indications and available treatment modalities. Currently, a dozen distinct complement‐specific therapeutics covering several intervention points are available in the clinic, benefiting patients suffering from eight disorders, not counting numerous clinical trials and off‐label uses. Observing this rapid rise of complement‐targeted therapy from obscurity to mainstream with amazement, one might ask whether the peak of this development has now been reached or whether the field will continue marching on to new heights. This review looks at the milestones of complement drug discovery and development achieved so far, surveys the currently approved drug entities and indications, and ventures a glimpse into the future advancements yet to come.

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Complement-regulatory biomaterial coatings: Activity and selectivity profile of the factor H-binding peptide 5C6

Cited by 9 publications

References 56 publications

Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro

Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro

The complement system: A key player in the host response to infections

Complement‐targeted therapeutics: Are we there yet, or just getting started?

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