TY - JOUR
T1 - Genomic and proteomic microglial profiling
T2 - Pathways for neuroprotective inflammatory responses following nerve fragment clearance and activation
AU - Glanzer, Jason G.
AU - Enose, Yoshimi
AU - Wang, Tong
AU - Kadiu, Irena
AU - Gong, Nan
AU - Rozek, Wojciech
AU - Liu, Jianuo
AU - Schlautman, Joshua D.
AU - Ciborowski, Pawel S.
AU - Thomas, Mark P.
AU - Gendelman, Howard E.
PY - 2007/8
Y1 - 2007/8
N2 - Microglia, a primary immune effector cell of the central nervous system (CNS) affects homeostatic, neuroprotective, regenerative and degenerative outcomes in health and disease. Despite these broad neuroimmune activities linked to specific environmental cues, a precise cellular genetic profile for microglia in the context of disease and repair has not been elucidated. To this end we used nucleic acid microarrays, proteomics, immunochemical and histochemical tests to profile microglia in neuroprotective immune responses. Optic and sciatic nerve (ON and SN) fragments were used to stimulate microglia in order to reflect immune consequences of nervous system injury. Lipopolysaccharide and latex beads-induced microglial activation served as positive controls. Cytosolic and secreted proteins were profiled by surface enhanced laser desorption ionization-time of flight (SELDI-TOF) ProteinChip®, 1D and 2D difference gel electrophoresis. Proteins were identified by peptide sequencing with tandem mass spectrometry, ELISA and western blot tests. Temporal expression of pro-inflammatory cytokines, antioxidants, neurotrophins, and lysosomal enzyme expression provided, for the first time, a unique profile of secreted microglia proteins with neuroregulatory functions. Most importantly, this molecular and biochemical signature supports a broad range of microglial functions for debris clearance and promotion of neural repair after injury.
AB - Microglia, a primary immune effector cell of the central nervous system (CNS) affects homeostatic, neuroprotective, regenerative and degenerative outcomes in health and disease. Despite these broad neuroimmune activities linked to specific environmental cues, a precise cellular genetic profile for microglia in the context of disease and repair has not been elucidated. To this end we used nucleic acid microarrays, proteomics, immunochemical and histochemical tests to profile microglia in neuroprotective immune responses. Optic and sciatic nerve (ON and SN) fragments were used to stimulate microglia in order to reflect immune consequences of nervous system injury. Lipopolysaccharide and latex beads-induced microglial activation served as positive controls. Cytosolic and secreted proteins were profiled by surface enhanced laser desorption ionization-time of flight (SELDI-TOF) ProteinChip®, 1D and 2D difference gel electrophoresis. Proteins were identified by peptide sequencing with tandem mass spectrometry, ELISA and western blot tests. Temporal expression of pro-inflammatory cytokines, antioxidants, neurotrophins, and lysosomal enzyme expression provided, for the first time, a unique profile of secreted microglia proteins with neuroregulatory functions. Most importantly, this molecular and biochemical signature supports a broad range of microglial functions for debris clearance and promotion of neural repair after injury.
KW - Cathepsins
KW - Microglia
KW - NFκB
KW - Neurotrophins
KW - Optic nerve
KW - Proteomics
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U2 - 10.1111/j.1471-4159.2007.04568.x
DO - 10.1111/j.1471-4159.2007.04568.x
M3 - Article
C2 - 17442053
AN - SCOPUS:34447320454
SN - 0022-3042
VL - 102
SP - 627
EP - 645
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 3
ER -