Release of the neuronal glycoprotein ICAM-5 in serum after hypoxic-ischemic injury.
Intercellular adhesion molecule (ICAM)-5 (telencephalin) is unique among the ICAMs, because it is only expressed in somatodendritic membranes of telencephalic neurons. To investigate the fate of ICAM-5 during focal brain injury, we induced hypoxia-ischemia (HI) damage in adult mice by right common carotid artery ligation followed by hypoxia. ICAM-5 was detectable in serum within a 48-hour window after HI injury. In HI brain, dendritic ICAM-5 immunore-activity was abolished, but it was present in the neuropil and soma of hippocampal pyramidal, dentate granule, and some cortical and striatal neurons. After HI injury, levels of ICAM-5 protein and messenger RNA initially increased, and ICAM-5 messenger RNA expression then decreased, although protein levels continued to increase. Because HI injury induces microglial activation with increases in CD11a/CD18 (lymphocyte function antigen [LFA]-1) counterreceptors to ICAM-5, we investigated whether modulation of interactions between LFA-1 receptors and brain ICAM-5 during HI injury are associated with changes in levels of serum ICAM-5. Intracerebroventricular administration of lipopolysaccharide to activate microglia before HI injury resulted in elevated serum ICAM-5 levels compared with those in mice with only HI injury. Pretreatment with anti-LFA-1 antibodies before HI injury or LFA-1 receptor knockout mice with HI injury had markedly reduced levels of serum ICAM-5. Lipopolysaccharide levels increased, whereas LFA-1 receptor blockade or LFA-1 knockout decreased HI injury in the first 12 hours. These data suggest that during the necrotic phase of HI injury, serum ICAM-5 may be a potential marker for somatodendritic neuronal damage.
Guo
H
H
Department of Neurology, University of Rochester Medical Center, NY, USA.
Tong
N
N
Turner
T
T
Epstein
L G
LG
McDermott
M P
MP
Kilgannon
P
P
Gelbard
H A
HA
D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D020925:Hypoxia-Ischemia, Brain / Q000097:blood* / Q000276:immunology*; D015151:Immunoblotting; D007136:Immunoglobulins / Q000097:blood* / Q000276:immunology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000276:immunology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000097:blood* / Q000276:immunology*; D013997:Time Factors
C504585:Icam5 protein, mouse; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins