Leukocyte recruitment and neuroglial activation during facial nerve regeneration in ICAM-1-deficient mice: effects of breeding strategy.
Intercellular adhesion molecule 1 (ICAM-1) is a widely expressed glycoprotein involved in leukocyte extravasation and the interaction of lymphocytes with antigen-presenting cells. We examined these aspects of ICAM-1 function in the central nervous system after axonal injury in wild-type and ICAM-1-deficient mice. ICAM-1 immunoreactivity in the normal mouse facial nucleus was restricted to the vascular endothelium. Transection of the facial nerve led to a fast upregulation of ICAM-1 on activated microglia in the axotomized facial nucleus and the infiltration of ICAM-1-positive lymphocytes. Labeling elsewhere was unchanged. In homozygous ICAM-1 mutant mice, ICAM-1 was absent from endothelial cells and lymphocytes, but low levels of ICAM-1 were detected on cell membranes of reactive microglial cells. Comparison of wild-type animals with homozygously bred, ICAM-1-deficient mice showed a reduction of astrocytic and microglial activation, massive late axonal sprouting, and decreased lymphocyte infiltration. These experiments were repeated in F1 progeny of heterozygous mice on a C57BL/6 background. Neuroglial activation and lymphocyte infiltration in F1 homozygously deficient mice was unaffected compared with wild-type siblings. The invading ICAM-1-deficient lymphocytes also adhered to the ICAM-1-positive phagocytotic microglial cells in the ICAM-1 mutants. No change in the recruitment of macrophages and granulocytes into the crushed facial nerve, and no effect on axonal regeneration occurred. These data argue against the requirement of endothelial ICAM-1 in the recruitment of leukocytes into the crushed peripheral nerve or the axotomized facial motor nucleus and stress the importance of adequately matched controls in studying the effects of gene deletion in experimental animals.
Werner
A
A
Department of Neuromorphology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Martin
S
S
Gutierrez-Ramos
J C
JC
Raivich
G
G
D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001369:Axons / Q000502:physiology; D019771:Axotomy; D001947:Breeding; D002634:Chemotaxis, Leukocyte; D005091:Exons; D005154:Facial Nerve / Q000166:cytology / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006579:Heterozygote; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics*; D007797:Laminin / Q000032:analysis; D007962:Leukocytes / Q000737:chemistry / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology*; D009046:Motor Neurons / Q000737:chemistry / Q000648:ultrastructure; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000276:immunology*
D007797:Laminin; D018799:Intercellular Adhesion Molecule-1