AIF-1 expression defines a proliferating and alert microglial/macrophage phenotype following spinal cord injury in rats.
Microglial cells are among the first and dominant cell types to respond to CNS injury. Following calcium influx, microglial activation leads to a variety of cellular responses, such as proliferation and release of cytotoxic and neurotrophic mediators. Allograft inflammatory factor-1, AIF-1 is a highly conserved EF-handed, putative calcium binding peptide, associated with microglia activation in the brain. Here, we have analyzed the expression of AIF-1 following spinal cord injury at the lesion site and at remote brain regions. Following spinal cord injury, AIF-1+ cells accumulated in parenchymal pan-necrotic areas and perivascular Virchow-Robin spaces. Subsequent to culmination at day 3--a situation characterized by infiltrating blood borne macrophages and microglia activation--AIF-1+ cell numbers decreased until day 7. In remote areas of Wallerian degeneration and delayed neuronal death, a more discrete and delayed activation pattern of AIF-1+ microglia/macrophages reaching maximum levels at day 14 was observed. There was a considerable match between AIF-1+ cells and PCNA (proliferating cell nuclear antigen) or Ki-67+ labeled cells. AIF-1 expression preceded the expression of ED1, thus indicating a pre-phagocytic role. It appears that AIF-1+ microglia/macrophages are among the earliest cells to respond to spinal cord injury. Our results suggest a role of AIF-1 in the initiation of the early microglial response leading to activation and proliferation essential for the acute response to CNS injury. AIF-1 might modulate microgliosis influencing the efficacy of tissue debris removal, myelin degradation, recruitment of oligodendrocytes and re-organisation of the CNS architecture.
Schwab
J M
JM
Institute of Brain Research, University of Tuebingen, Medical School, Calwer Str. 3, D-72076, Tuebingen, Germany. jmschwab@med.uni-tuebingen.de
Frei
E
E
Klusman
I
I
Schnell
L
L
Schwab
M E
ME
Schluesener
H J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000378:metabolism
C100745:Aif1 protein, rat; D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins