Inhibition of leukocyte locomotion and chemotaxis by lipid-specific bacterial toxins

Abstract

SINCE a number of cytolytic bacterial protein toxins have specific actions on individual membrane lipids, these toxins, used at sub-toxic doses, should be useful for exploring the role of lipids in membrane-activated cell functions. I have suggested^1–3 that leukocyte chemotactic factors initiate a locomotor response by virtue of their ability to penetrate the hydrophobic interior of the lipid bilayei of the cell membrane, and thus possibly to bring about changes in the intracytoplasmic concentration of divalent cations and activation of contractile systems in the cytoplasm. If this is so, it may be possible to modify locomotor and chemotactic responses in leukocytes using lipid-specific toxins. The oxygen-labile lysins such as streptolysin 0 or Clostridium perfringens θ toxin show a specific affinity for cell membrane cholesterol. Bacterial phospholipases C attack the polar heads of a number of membrane phospholipids⁴. Among those phospholipases, sphingomyelinase C, the β toxin of Staphylococcus aureus, shows a high substrate specificity for sphingomyelin⁵. Here I show that the locomotor responses of leukocytes to chemoattractants are modified by these toxins and that neutrophils show a different pattern of response from monocytes. The locomotor response of human blood monocytes is inhibited by Cl. perfringens phospholipase C (PLC) and by sphingomyelinase C but not by Cl. perfringens θ toxin. In contrast, the response of human blood neutrophils is inhibited by θ toxin but not by phospholipases C.