Repression of phagocytosis by human CD33 is not conserved with mouse CD33.
Abhishek BhattacherjeeEmily RodriguesJaesoo JungMatthew Luzentales-SimpsonJhon R EnterinaDanny GalleguillosChris D St LaurentMaryam Nakhaei-NejadFelix F FuchsbergerLaura StreithQian WangNorihito KawasakiShiteng DuanArjun BainsJames C PaulsonChristoph RademacherFabrizio GiulianiSimonetta SipioneMatthew Scott MacauleyPublished in: Communications biology (2019)
CD33 is an immunomodulatory receptor linked to Alzheimer's disease (AD) susceptibility via regulation of phagocytosis in microglia. Divergent features between human CD33 (hCD33) and murine CD33 (mCD33) include a unique transmembrane lysine in mCD33 and cytoplasmic tyrosine in hCD33. The functional consequences of these differences in restraining phagocytosis remains poorly understood. Using a new αmCD33 monoclonal antibody, we show that mCD33 is expressed at high levels on neutrophils and low levels on microglia. Notably, cell surface expression of mCD33 is entirely dependent on Dap12 due to an interaction with the transmembrane lysine in mCD33. In RAW264.7 cultured macrophages, BV-2 cultured microglia, primary neonatal and adult microglia, uptake of cargo - including aggregated Aβ1-42 - is not altered upon genetic ablation of mCD33. Alternatively, deletion of hCD33 in monocytic cell lines increased cargo uptake. Moreover, transgenic mice expressing hCD33 in the microglial cell lineage showed repressed cargo uptake in primary microglia. Therefore, mCD33 and hCD33 have divergent roles in regulating phagocytosis, highlighting the importance of studying hCD33 in AD susceptibility.
Keyphrases
- inflammatory response
- endothelial cells
- neuropathic pain
- monoclonal antibody
- lps induced
- lipopolysaccharide induced
- cell surface
- single cell
- induced pluripotent stem cells
- poor prognosis
- gene expression
- stem cells
- spinal cord injury
- cognitive decline
- pluripotent stem cells
- cell therapy
- nk cells
- binding protein
- copy number
- mild cognitive impairment