BETA-4 INTEGRIN AND OTHER SCHWANN-CELL MARKERS IN AXONAL NEUROPATHY

Schwann cell gene expression is dynamically regulated after peripheral nerve injury and during regeneration. We hypothesized that the change s in protein expression described after rat peripheral nerve injury co uld be used to identify single Schwann cell-axon units in human axonal neuropathy Therefore, we performed immuno-fluorescence staining on se ctions of injured rat sciatic nerves compared with sections of neuropa thic human sural nerves. We chose the markers beta 4 integrin, PO glyc oprotein, and glial fibrillary acidic protein (GFAP) to characterize S chwann cells, and neurofilament-heavy (NF-H) to recognize axons. Norma l rat or human myelin-forming units demonstrated a sharp ring of beta 4 staining at their outer surface, PO staining in the myelin sheath, a nd NF-H staining in the axon. Acutely denervated rat units transited f rom broken rings of beta 4 and PO staining, to diffuse beta 4 and abse nt PO and NF-H staining. Chronically denervated rat Schwann cells re-e xpressed beta 4 more highly, but in a diffuse, non-polarized pattern. In contrast, regenerating units re-expressed beta 4, PO, and NF-H; bet a 4 staining was polarized to the outer surface of Schwann cells. Fina lly, GFAP staining increased progressively after injury and decreased during regeneration in the distal nerve stump. In neuropathic human su ral nerves, we identified units exhibiting each of these beta 4, PO, a nd NF-H staining patterns; the proportion of each pattern correlated b est with the extent and chronicity of axonal injury. Thus, synchronous injury of rat sciatic nerve predicts patterns of Schwann cell marker expression in human axonal neuropathy. In addition, the unique changes in the polarity of beta 4 integrin expression, in combination with ch anges in PO and NF-H expression, may distinguish normal from denervate d or reinnervated myelin-forming Schwann cells in human sural nerve bi opsies. (C) 1996 Wiley-Liss, Inc.