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E L Becker

Publications and source records attributed to E L Becker.

At least 181 records · Page 10Linked to original sources
PubMed1969

The requirement of serine esterase function in complement-dependent erythrophagocytosis.

The p-nitrophenyl ethyl phosphonate esters have been shown to inhibit complement-dependent erythrophagocytosis when exposed to guinea pig polymorphonuclear leukocytes prior to the initiation of phagocytosis. Inhibition of phagocytosis occurred in a manner characteristic of the well-defined capacity of phosphonate esters to inactivate serine esterases: inhibition was irreversible, dependent upon the temperature of reaction and pH of the reaction medium, and proportional to the concentration of inhibitor used and the duration of exposure between leukocytes and inhibitor. Phosphonate inhibition was further shown to be independent of any general cell damaging effects of the compounds used. The phagocytic enzyme inhibited by phosphonate esters apparently exists in or on leukocytes in an already activated state prior to the initiation of the phagocytic process. The inhibitory profile of the activated phagocytic esterase was found to be essentially identical to the profile of inhibition previously obtained for the activated chemotactic esterase of rabbit polymorphonuclear leukocytes, suggesting that the same enzyme may function in both chemotaxis and phagocytosis. Various substrates including acetate esters reported to protect the activated chemotactic esterase from inhibition by phosphonate esters did not exhibit a clear protective effect in the phagocytic system and attempts to define the relationship between the two enzymes were unsuccessful. Suggestive evidence was also obtained for the requirement of the function of a second, activatable esterase in the phagocytic process.

Animals↗
PubMed1969

Esterases of the polymorphonuclear leukocyte capable of hydrolyzing acetyl DL-phenyl-alanine beta-naphthyl ester. Relationship to the activatable esterase of chemotaxis.

Previous published work has led to the hypothesis that the activatable esterase of chemotaxis is a serine esterase of the rabbit polymorphonuclear leukocyte existing in an inert, phosphonate insusceptible form, which after activation is capable of hydrolyzing aromatic amino acid esters and being inhibited by phosphonates. In the present study, directed to the testing of this hypothesis, we have shown that rabbit peritoneal polymorphonuclear leukocytes contain three esterases capable of hydrolyzing the aromatic amino acid ester, acetyl DL-phenylalanine beta-naphthyl ester. Two of these esterases, esterase 1 and esterase 2, are inhibited by various p-nitrophenyl ethyl phosphonate esters. The inhibition of each esterase is irreversible and progressive with time. When the logarithm of the esterase activity remaining after cell and inhibitor have been in contact for a constant time is plotted against the concentration of inhibitor, a straight line results. These results support the conclusion that both esterases are serine esterases. The third esterase, esterase 3, differs from the other two by its inability to be inactivated by any of the phosphonates no matter how high the concentration of phosphonate or prolonged the period of incubation of cell with phosphonate. The activity of esterase 1 is at least 10,000 times more easily inhibited by phosphonates than is that of esterase 2; incubating rabbit polymorphonuclear leukocytes for 15 min at 27 degrees C with 10(-9)-10(-8)M concentrations of various phosphonates inactivates esterase 1, but it required 10(-6)-10(-4)M concentrations of the same phosphonates to inhibit esterase 2. The inhibition profiles of esterase 1 are distinctly different from those of esterase 2 when the two esterases are tested with the phenylalkylphosphonates, chloroalkylphosphonates, and alkylphosphonates. The inhibition profile of esterase 1 is essentially the same as that of the activatable esterase of chemotaxis obtained previously when the same three homologous series of phosphonates were tested for their ability to protect against deactivation by the chemotactic factor or give chemotactic-dependent inhibition. It is tentatively concluded that esterase 1 of the rabbit peritoneal neutrophil is the activated form of the activatable esterase of chemotaxis.

Animals↗
PubMed1968

The deactivation of rabbit neutrophils by chemotactic factor and the nature of the activatable esterase.

As shown previously, immune complexes engender in rabbit serum a factor capable of inducing chemotaxis of rabbit polymorphonuclear leukocytes. This chemotactic factor consists of a complex of the fifth, sixth, and seventh components of complement. As demonstrated here, the polymorphonuclear leukocytes incubated with such treated rabbit serum lose their ability to respond chemotactically to the chemotactic factor. They are "deactivated." The process of "deactivation" is a function of the duration of contact of the cells with, and the concentration of, the treated serum. There is a parallelism between the time course of deactivation and of chemotaxis, as well as the dose-response curves for the two processes. Chemotactic factor purified by isoelectric precipitation and ion-exchange chromatography produces deactivation in the same manner as the treated serum. The deactivating activity requires, as does the chemotactic factor, the sixth component of complement; like the chemotactic factor, it is heat-stable and nondialyzable. Deactivation is prevented by the same phosphonate esters shown previously to prevent chemotaxis by the complement-associated chemotactic factor. The profiles of the phosphonates in protecting against deactivation are the same as the profiles for the chemotactic factor-dependent inhibition of chemotaxis. Aromatic amino acid derivatives prevent both chemotaxis and deactivation. We conclude from this evidence that the chemotactic factor is able to deactivate or induce chemotaxis depending upon experimental conditions. The fact that the profiles given by the phosphonates for protection against chemotactic factor-dependent deactivation and for chemotactic factor-dependent inhibition of chemotaxis are the same indicates that the "activatable esterase" is involved in both processes. Acetate esters such as ethyl acetate and others shown previously to prevent chemotaxis by inhibiting the "activated esterase" do not prevent deactivation. This indicates that deactivation can occur without participation of the latter enzyme, implying that deactivation involves only a part of the biochemical mechanism of chemotaxis. The protection against deactivation afforded by aromatic amino acid derivatives is specific, insofar as nonaromatic amino compounds and simple acetate esters have no effect. In addition, as stated, the aromatic amino acid derivatives inhibit deactivation and chemotaxis by the chemotactic factor. This latter finding, together with the demonstration of the involvement of the activatable esterase in both deactivation and chemotaxis, suggests that the activatable esterase of the rabbit polymorphonuclear leukocyte is a serine esterase with a special affinity for aromatic amino acid derivatives.

Acetates↗