Institute of Medical Microbiology and Hygiene, University of Mainz; and
* Institute of Physiology I, University of Tuebingen, Germany
Correspondence: Institute of Medical Microbiology and Hygiene, Hochhaus am Augustusplatz, D-55101 Mainz, Germany. E-mail: makowiec{at}mail.uni-mainz.de
Cleavage of membrane-associated L-selectin regulates leukocyte rolling on vascular endothelium at sites of inflammation. We report that rapid and massive shedding of L-selectin occurs from granulocytes attacked by the pore-forming bacterial toxin streptolysin O (SLO). Shedding was not induced by an SLO mutant that retained binding capacity but lacked pore-forming activity. Cells permeabilized with SLO exhibited a 1.5-fold increase in the activity of neutral sphingomyelinase, which was accompanied by increased ceramide formation. L-selectin cleavage was inducible by treatment of cells with bacterial sphingomyelinase, and also through exogenous application of a cell-permeable ceramide analog. Our data identify a novel path to the shedding process and show that activation of neutral sphingomyelinase with the generation of ceramide is an important event underlying enhanced sheddase function in cells permeabilized by a pore-forming toxin.
Key Words: neutrophils • shedding • bacterial toxin
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