Inhibition of the adhesion step of leukodiapedesis: a critical event in the recovery of Guillain-Barre syndrome associated with accumulation of proteolytically active lymphocytes in blood

Intraneural inflammation, that reflects emigration of immune cells from blo od to nerve tissue, is a critical event in Guillain-Barre syndrome pathogen esis. To investigate the adhesion and transmigration phases of leukodiapede sis, we determined in a series of patients with GBS: (1) circulating levels of soluble forms of adhesion molecules (sICAM-1 and sVCAM-1); (2) attachme nt capacities of circulating lymphocytes to rICAM-1 and rVCAM-1; (3) fibron ectin-penetrating capacities of circulating lymphocytes; and (4) lymphocyte intracellular concentrations of MMP-9 at the different phases of GBS and i n healthy controls. Circulating levels of sVCAM-1 and sICAM-1 were above no rmal values at the time of progression, markedly increased at the rime of p lateau (sVCAM-1: P<0.03; sICAM-1: P<0.02), and tended to normalize during r ecovery. The percentage of cells with attachment capacities to rVCAM-1 and to rICAM-1 decreased from progression to recovery by 30 and 31%, respective ly (P<0.02). The number of circulating lymphocytes with fibronectin penetra ting capacities was lower than controls at the time of progression (P<0.01) , then progressively increased to reach values higher than controls at the time of late recovery (P<0.02). Cellular concentrations of MMP-9 in circula ting lymphocytes paralleled their fibronectin penetrating capacities. These results suggest early emigration of lymphocytes into nerve, followed by sh edding of adhesion molecules from endothelium, and late decrease of lymphoc yte adhesion capacities. Plateau and recovery are associated with accumulat ion in the vascular compartment of still proteolytically active lymphocytes that can no longer adhere to endothelial cells. Modulation of the adhesion step of leukodiapedesis may be crucially involved in the switch from progr ession to plateau of GBS. <(c)> 2001 Elsevier Science B.V. All rights reser ved.