Control of leukocyte functions. Role of internal H+ concentration and a membrane-bound esterase.
An activable membrane-bound neutral esterase which responds to many of the known leukocyte cytotaxins and appears to be involved in several membrane functions of these cells is described. Activation of this enzyme is associated with excretion of H+, O2-, and lysosomal enzymes; aggregation of intact cells and isolated membranes; activation of glucose oxidation; and changes in cellular motility. Conditions which alter the activity of this enzyme, e.g., addition of H+ or of synthetic hydrophobic peptides or esters (whose hydrolysis liberates H+ within or on these membranes) or by repeated washing of the cells (which partially removes this enzyme from the cells), all markedly alter rates of the above cellular functions. Although the native membrane substrate for this enzyme is not yet identified, the enzyme appears not to be involved in gamma-glutamyl transpeptidase reactions. Rather the data support the concept that hydrolysis by the enzyme of membrane components (proteins) results in H+ and O2- efflux (as well as other cation fluxes) with resultant rise in intracellular pH. Under these conditions cell movement ceases. Agents, e.g., low concentrations of chemotactic peptides or proteins which inhibit H+ and O2- excretion accelerate motility. The presence of external hydrophobic substrates for this enzyme, whose hydrolysis liberates H+ in or on these membranes and also inhibits efflux of H+ and O2-, also optimizes motility. The esterase(s) thus appears to control many functions of these cells by controlling H+ efflux from these cells.
D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation; D004950:Esterases / Q000097:blood*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000502:physiology; D013501:Surface-Active Agents / Q000494:pharmacology
D013501:Surface-Active Agents; D004950:Esterases