Organophosphorus inhibition of lysosomal enzyme secretion from polymorphonuclear leucocytes. Evidence of a lack of a requirement for esterase activation.
Previously, di-isopropylphosphorofloridate (DFP) was shown to inhibit the release of lysosomal enzymes induced by chemotactic factors. It was suggested that the inhibition was due to the phosphorylation of a cell bound serine esterase activated by the chemotactic factor. However, as shown here, di-isopropyl methyl phosphate, a nonphosphorylating analogue of DFP, inhibits just as well as DFP, the release of lysozyme and beta glucuronidase from rabbit polymorphonuclear leucocytes induced by chemotactic factor in the presence of cytochalasin B. Similarly, the poorly phosphorylating phenyl ethyl pentylphosphonate and phenyl ethyl phenylpropylphosphonate inhibit enzyme release, induced under the same conditions, as well as or better than the corresponding good phosphorylators, p-nitropheny ethyl pentylphosphonate and p-nitrophenyl ethyl phenylpropylphosphonate. Phenyl ethyl pentylphosphonate inhibits at least as well or probably better than p-nitrophenyl ethyl pentyl phosphonate, the chemotactic factor induced relase of lysozyme from polymorphonuclear leucocytes spread on Millipore filters in the absence of cytochalasin B. We conclude that, under the circumstances tested, there is no evidence that the release of lysosomal enzymes from rabbit peritoneal polymorphonuclear leucocytes induced by chemotactic factor involves the activation of an esterase.
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003571:Cytochalasin B; D004789:Enzyme Activation; D004950:Esterases / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism*; D007531:Isoflurophate / Q000494:pharmacology; D009113:Muramidase / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010766:Phosphorylation; D011817:Rabbits; D012636:Secretory Rate / Q000187:drug effects
D009943:Organophosphorus Compounds; D007531:Isoflurophate; D003571:Cytochalasin B; D004950:Esterases; D009113:Muramidase; D005966:Glucuronidase