Factor H

Background

Factor H is pivotal in regulating the alternative complement pathway, essential for safeguarding host cells, particularly in renal tissues. It performs dual roles:

1) Regulating the assembly and disassembly of the alternative pathway C3/C5 convertase;

2) Serving as a cofactor for factor I, which enzymatically degrades C3b bound to factor H.

Clinical conditions linked to factor H encompass factor H deficiency and age-related macular degeneration, highlighting its critical role in immune homeostasis and disease susceptibility.

Its Gene ID: 3075, UniProtKB ID: P08603, and OMIM ID: 134370.

Factor H in Complement Pathways

Factor H, a glycoprotein pivotal in immune regulation, maintains equilibrium by modulating complement activation. It functions as a soluble inhibitor, binding to endogenous markers like glycan structures to arrest the activation and amplification of complement on cellular surfaces. Accelerating the decay of the alternative pathway C3 convertase C3bBb impedes the localized buildup of C3b, which is pivotal in the cascade of complement amplification. Factor H's interaction with C3b also regulates C5 convertases. Moreover, it mediates cellular responses via specific receptors like CR3/ITGAM, facilitating the adhesion of human neutrophils to pathogens and subsequent phagocytosis and elimination of these invaders.

Fig.1 Factor H in complement pathways and factor H protein family.¹

Factor H-Based Products Utilizations

Anti-Factor H Antibody Application in AMD Therapy Research

Age-related macular degeneration (AMD) ranks globally among the primary causes of vision loss. Scientists have investigated retinal tissue using a mouse model of NaIO3-induced retinal pigment epithelium (RPE) atrophy to clarify its pathology. Techniques such as western blot, multiplex ELISA, immunohistochemistry (including anti-factor H antibody), qRT-PCR, and RNA sequencing are utilized. NaIO₃ treatment results in patchy RPE loss and photoreceptor layer thinning. Additionally, increased retinal expression and deposition of complement components like factor H. Proinflammatory factor transcripts are elevated, while VEGF-A mRNA levels decrease. These findings indicate that local immune responses are crucial in retinal degeneration.

Fig.2 Immunohistochemical staining of factor H in the neurosensory retina of NaIO₃-treated mice.²

Complement Factor H as a Potential Therapeutic Target in RA

To investigate the role and mechanism of complement factor H in rheumatoid arthritis (RA)-related peripheral and joint inflammation, researchers have measured factor H levels in serum and synovial fluid using ELISA. Pyroptosis of monocytes is assessed via western blotting and flow cytometry, and ELISA tests inflammatory cytokine release. Cell migration and invasion of fibroblast-like synoviocytes (FLS) are evaluated using wound healing and transwell assays. RNA sequencing has identified potential factor H targets. Factor H and TNF-α reduce cell death and inflammatory cytokine release in RA monocytes. Factor H inhibits migration, invasion, and TNF-α-induced proinflammatory cytokines and MMPs in RA FLS. Factor H exhibits anti-inflammatory effects, suggesting its potential as a therapeutic target for RA.

Creative Biolabs provides an extensive range of products centered on complement factor H, including assay kits, recombinant proteins, protein lysates, and antibodies directed against factor H. Our offerings extend to custom-designed factor H-specific products, such as bespoke bispecific antibody solutions crafted to address individualized needs and specifications.

References

1. Józsi, Mihály. "Factor H family proteins in complement evasion of microorganisms." Frontiers in Immunology 8 (2017): 571.
2. Enzbrenner, Anne, et al. "Sodium iodate-induced degeneration results in local complement changes and inflammatory processes in murine retina." International journal of molecular sciences 22.17 (2021): 9218.