α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State.
Anti-inflammatory
Cytokines
Immunomodulation
Microglia
Spinal cord injury
α-gal
Journal
Tissue engineering and regenerative medicine
ISSN: 2212-5469
Titre abrégé: Tissue Eng Regen Med
Pays: Korea (South)
ID NLM: 101699923
Informations de publication
Date de publication:
15 Dec 2023
15 Dec 2023
Historique:
received:
06
07
2023
accepted:
30
10
2023
revised:
21
10
2023
medline:
15
12
2023
pubmed:
15
12
2023
entrez:
15
12
2023
Statut:
aheadofprint
Résumé
Macrophages and microglia play critical roles after spinal cord injury (SCI), with the pro-healing, anti-inflammatory (M2) subtype being implicated in tissue repair. We hypothesize that promoting this phenotype within the post-injured cord microenvironment may provide beneficial effects for mitigating tissue damage. As a proof of concept, we propose the use of nanoparticles incorporating the carbohydrate antigen, galactose-α-1,3-galactose (α-gal epitope) as an immunomodulator to transition human microglia (HMC3) cells toward a pro-healing state. Quiescent HMC3 cells were acutely exposed to α-gal nanoparticles in the presence of human serum and subsequently characterized for changes in cell shape, expression of anti or pro-inflammatory markers, and secretion of phenotype-specific cytokines. HMC3 cells treated with serum activated α-gal nanoparticles exhibited rapid enlargement and shape change in addition to expressing CD68. Moreover, these activated cells showed increased expression of anti-inflammatory markers like Arginase-1 and CD206 without increasing production of pro-inflammatory cytokines TNF-α or IL-6. This study is the first to show that resting human microglia exposed to a complex of α-gal nanoparticles and anti-Gal (from human serum) can be activated and polarized toward a putative M2 state. The data suggests that α-gal nanoparticles may have therapeutic relevance to the CNS microenvironment, in both recruiting and polarizing macrophages/microglia at the application site. The immunomodulatory activity of these α-gal nanoparticles post-SCI is further described in the companion work (Part II). Resting microglia subjected to α-gal nanoparticle treatment in the presence of anti-Gal (found in serum) become activated and exhibit pro-healing phenotypic markers (Arginase-1, CD206) and secrete VEGF. Expression of pro-inflammatory markers (IL-6, TNF-α) was concomitantly reduced.
Sections du résumé
BACKGROUND
BACKGROUND
Macrophages and microglia play critical roles after spinal cord injury (SCI), with the pro-healing, anti-inflammatory (M2) subtype being implicated in tissue repair. We hypothesize that promoting this phenotype within the post-injured cord microenvironment may provide beneficial effects for mitigating tissue damage. As a proof of concept, we propose the use of nanoparticles incorporating the carbohydrate antigen, galactose-α-1,3-galactose (α-gal epitope) as an immunomodulator to transition human microglia (HMC3) cells toward a pro-healing state.
METHODS
METHODS
Quiescent HMC3 cells were acutely exposed to α-gal nanoparticles in the presence of human serum and subsequently characterized for changes in cell shape, expression of anti or pro-inflammatory markers, and secretion of phenotype-specific cytokines.
RESULTS
RESULTS
HMC3 cells treated with serum activated α-gal nanoparticles exhibited rapid enlargement and shape change in addition to expressing CD68. Moreover, these activated cells showed increased expression of anti-inflammatory markers like Arginase-1 and CD206 without increasing production of pro-inflammatory cytokines TNF-α or IL-6.
CONCLUSION
CONCLUSIONS
This study is the first to show that resting human microglia exposed to a complex of α-gal nanoparticles and anti-Gal (from human serum) can be activated and polarized toward a putative M2 state. The data suggests that α-gal nanoparticles may have therapeutic relevance to the CNS microenvironment, in both recruiting and polarizing macrophages/microglia at the application site. The immunomodulatory activity of these α-gal nanoparticles post-SCI is further described in the companion work (Part II). Resting microglia subjected to α-gal nanoparticle treatment in the presence of anti-Gal (found in serum) become activated and exhibit pro-healing phenotypic markers (Arginase-1, CD206) and secrete VEGF. Expression of pro-inflammatory markers (IL-6, TNF-α) was concomitantly reduced.
Identifiants
pubmed: 38099990
doi: 10.1007/s13770-023-00613-1
pii: 10.1007/s13770-023-00613-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : 1R21NS115094-01
Pays : United States
Informations de copyright
© 2023. Korean Tissue Engineering and Regenerative Medicine Society.
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