The chemokine fractalkine in patients with severe traumatic brain injury and a mouse model of closed head injury.
The potential role of the chemokine Fractalkine (CX3CL1) in the pathophysiology of traumatic brain injury (TBI) was investigated in patients with head trauma and in mice after experimental cortical contusion. In control individuals, soluble (s)Fractalkine was present at low concentrations in cerebrospinal fluid (CSF) (12.6 to 57.3 pg/mL) but at much higher levels in serum (21,288 to 74,548 pg/mL). Elevation of sFractalkine in CSF of TBI patients was observed during the whole study period (means: 29.92 to 535.33 pg/mL), whereas serum levels remained within normal ranges (means: 3,100 to 59,159 pg/mL). Based on these differences, a possible passage of sFractalkine from blood to CSF was supported by the strong correlation between blood-brain barrier dysfunction (according to the CSF-/serum-albumin quotient) and sFractalkine concentrations in CSF (R = 0.706; P < 0.01). In the brain of mice subjected to closed head injury, neither Fractalkine protein nor mRNA were found to be augmented; however, Fractalkine receptor (CX3CR1) mRNA steadily increased peaking at 1 week postinjury (P < 0.05, one-way analysis of variance). This possibly implies the receptor to be the key factor determining the action of constitutively expressed Fractalkine. Altogether, these data suggest that the Fractalkine-CX3CR1 protein system may be involved in the inflammatory response to TBI, particularly for the accumulation of leukocytes in the injured parenchyma.
Rancan
Mario
M
Department of Trauma Surgery, The Alfred Hospital & Monash University, Melbourne, VIC, Australia. RancanMario@hotmail.com
Bye
Nicole
N
Otto
Vivianne I
VI
Trentz
Otmar
O
Kossmann
Thomas
T
Frentzel
Stefan
S
Morganti-Kossmann
Maria Cristina
MC
D000293:Adolescent; D000328:Adult; D000818:Animals; D001812:Blood-Brain Barrier; D001930:Brain Injuries / Q000276:immunology / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D016489:Head Injuries, Closed / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics; D015728:Receptors, HIV / Q000235:genetics; D012995:Solubility
D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015728:Receptors, HIV