Reactions Governed by Flux of Monovalent Ions

Two possibly related phenomena have been found to be dependent on the flux of monovalent ions. The hypothetical common link is represented by a newly discovered family of intracellular proteases whose activity may be influenced by concentrations. Interleukin converting enzyme (ICE) is the best studied member of this family. Efflux of from monocytes leads to activation of ICE, so that the cells rapidly process and export IL-16 (Walev etal., 1995). An ICE-related protease is involved in regulating programmed cell death, which may be the reason why formation of K -permissive pores by alpha-toxin in human T-lymphoctes causes apoptosis (Jonas et a/., 1994). Both apoptosis and ICE-activation are inhibited when alpha-toxin treated cells are suspended in K -rich medium. It is of interest that simultaneous flooding of cells with Ca , such as occurs when larger pores are formed in lymphocytes (e.g. at high alpha-toxin concentrations or with . coli hemolysin) counteracts the apoptosis-promoting effect of K -efflux (Jonas et a/., 1994). 

Many of these reactions are compositely triggered by a flux of extracellular Ca into the cells, combined with liberation of Ca from intracellular storage pools. The present discussion is oversimplified and will not take the latter event into account. 

Secretion. Exocytotic liberation of granular constituents has been demonstrated in leukocytes, platelets and neurological cells. Platelets attacked by alpha-toxin secrete platelet factor 4 and factor 5 (Arvand et a/., 1990 Bhakdi ef al., 1988). Release of the latter leads to assembly of platelet-bound prothrombinase complexes that generate thrombin. Alpha-toxin can thus promote coagulation via its perme-abilizing action on platelets. Release of granule constituents from leukocytes has been observed after permeabilization of these cells by HlyA. For example, large amounts of elastase are secreted into the extracellular medium (Bhakdi eta/., 1989). 

Generation of lipid mediators. Ca -dependent phospholipase activation has been shown to stimulate synthesis of lipid mediators derived from arachidonic acid. The production of these lipid mediators can provoke both short- and long-range effects on bystander cells (e.g. (Bhakdi eta/., 1994 Suttorp efal., 1985 Suttorp eta/., 1992). 

Cytoskeletal dysfunction. Ca -dependent cytoskeletal dysfunction has been observed in endothelial cells under attack by PFTs cellular contraction leads to formation of intercellular gaps causing leakage of macromolecules across a confluent monolayer (Suttorp eta/., 1990 Suttorp et al., 1988). 

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