Integrin family of cell adhesion molecules in the injured brain: regulation and cellular localization in the normal and regenerating mouse facial motor nucleus.
Integrins are a large family of heterodimeric glycoproteins that play a crucial role in cell adhesion during development, inflammation, and tissue repair. In the current study, we investigated the localization of different integrin subunits in the mouse facial motor nucleus and their regulation after transection of the facial nerve. In the normal mouse brain, there was clear immunoreactivity for alpha5-, alpha6-, and beta1-integrin subunits on blood vessel endothelia and for alphaM- and beta2-subunits on resting parenchymal microglia. Facial nerve transection led to an up-regulation of the beta1-subunit on the axotomized neurons and an increase in the alpha4-, alpha5-, alpha6-, beta1-, alphaM-, alphaX-, and beta2-subunits on the adjacent, activated microglia. Quantification of the microglial integrins revealed two different expression patterns. The subunits alpha5 and alpha6 showed a monophasic increase with a maximum at day 4, the alphaM-subunit a biphasic regulation, with an early peak at day 1 and an elevated plateau between day 14 and 42. At day 14, there was also an influx of lymphocytes immunoreactive for the alpha4beta1- and alphaLbeta2-integrins, which aggregated at sites of neural debris and phagocytotic microglia. This finding was accompanied by a significant increase of the alpha5beta1-integrin on blood vessel endothelia. In summary, facial axotomy is followed by a strong and cell-type-specific expression of integrins on the affected neurons and on surrounding microglia, lymphocytes, and vascular endothelia. The presence of several, strikingly different temporal patterns suggests a selective involvement of these molecules in the different adhesive events during regeneration in the central nervous system.
Department of Neuromorphology, Max-Planck Institute for Neurobiology, D-82152 Martinsried, Germany.
C U
CU
Kloss
A
A
Werner
M A
MA
Klein
J
J
Shen
K
K
Menuz
J C
JC
Probst
G W
GW
Kreutzberg
G
G
Raivich
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001253:Astrocytes / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000098:blood supply; D002448:Cell Adhesion; D019281:Dimerization; D004730:Endothelium, Vascular / Q000378:metabolism; D005154:Facial Nerve / Q000378:metabolism / Q000473:pathology; D020220:Facial Nerve Injuries; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation; D007091:Image Processing, Computer-Assisted; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009928:Organ Specificity; D010587:Phagocytosis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012183:Retrograde Degeneration; D013154:Spleen / Q000737:chemistry; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016023:Integrins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger