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 glycoprote in involved in leukocyte extravasation and the interaction of lymphocytes w ith 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-d eficient mice. ICAM-1 immunoreactivity in the normal mouse facial nucleus w as restricted to the vascular endothelium. Transection of the facial nerve led to a fast upregulation of ICAM-1 on activated microglia in the axotomiz ed facial nucleus and the infiltration of ICAM-1-positive lymphocytes. Labe ling elsewhere was unchanged. In homozygous ICAM-1 mutant mice, ICAM-1 was absent from endothelial cells and lymphocytes, but low levels of ICAM-1 wer e detected on cell membranes of reactive microglial cells. Comparison of wi ld-type animals with homozygously bred, ICAM-1-deficient mice showed a redu ction of astrocytic and microglial activation, massive late axonal sproutin g, and decreased lymphocyte infiltration. These experiments were repeated i n F1 progeny of heterozygous mice on a C57BL/6 background. Neuroglial activ ation and lymphocyte infiltration in F1 homozygously deficient mice was una ffected compared with wild-type siblings. The invading ICAM-1-deficient lym phocytes also adhered to the ICAM-1-positive phagocytotic microglial cells in the ICAM-1 mutants. No change in the recruitment of macrophages and gran ulocytes into the crushed facial nerve, and no effect on axonal regeneratio n occurred. These data argue against the requirement of endothelial ICAM-1 in the recruitment of leukocytes into the crushed peripheral nerve or the a xotomized facial motor nucleus and stress the importance of adequately matc hed controls in studying the effects of gene deletion in experimental anima ls.