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Biomedical subjects

E Schiffmann

Publications and source records attributed to E Schiffmann.

At least 73 records · Page 4Linked to original sources
PubMed1980

A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids.

When rabbit peritoneal neutrophils were treated with glucocorticoids, their chemotactic response to stimulation by the chemoattractant fMet-Leu-Phe was markedly reduced. Preincubation of cells with glucocorticoids also decreased phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) activity in situ as measured by the release of [1-14C]arachidonic acid previously incorporated into phospholipids. The inhibitory potencies of glucocorticoids on phospholipase A2 activity correlated well with their anti-inflammatory activities and their abilities to bind to glucocorticoid receptors. Inhibitors of RNA and protein synthesis suppressed the inhibitory effect of glucocorticoids on phospholipase A2 activity. Digestion of the glucocorticoid-treated cells by Pronase overcame the inhibitory activity. Phospholipase A2 activity induced by Ca2+ ionophore A23187 was not affected by Pronase treatment. Gel filtration of proteins from neutrophil membranes labeled with [3H]lysine showed an induction of protein(s) (about 40,000 daltons) after glucocorticoid treatment. This protein inhibited a partially purified pancreatic phospholipase A2 and reduced the peptide-initiated chemotactic response of neutrophils.

Animals↗
PubMed1980

Role of attachment factors and attractants in fibroblast chemotaxis.

Fibroblasts require both a collagen substratum and fibronectin for adherence and subsequent migration in the Boyden chamber. Both fibronectin and lymphokines are good chemoattractants, whereas the collagens are weaker. Fibroblasts appear to require cytoskeletal organization and methylation reactions for chemotaxis, properties shown previously for macrophages and neutrophils. Fibroblasts, however, migrate more slowly than phagocytic cells and appear to require protein synthesis.

Animals↗
PubMed1979

Chemoattractants stimulate degradation of methylated phospholipids and release of arachidonic acid in rabbit leukocytes.

When rabbit peritoneal leukocytes were treated with chemoattractants such as fMet-Leu-Phe, an apparent decrease of [3H]methyl incorporation into the lipid fraction from L-[methyl-3H]methionine was observed. This decrease was a result of increased degradation of methylated phospholipids, not of decreased synthesis. Chemotactic peptides did not affect the metabolism of the phospholipids in which [methyl-14C]choline was incorporated. The disappearance of the [3H]methyl group was associated with the release of [1-14C]arachidonic acid from phospholipids prelabeled with these compounds. These findings suggested the activation by chemoattractants of phospholipase A2, an enzyme that removes an unsaturated fatty acid from phospholipids. The order of potency of chemoattractants for the stimulated degradation of phospholipids was in good agreement with that for chemotaxis. Mepacrine (quinacrine) and hydrocortisone inhibited and a phorbol ester enhanced both chemotaxis and phospholipase A2 activity. These results, taken together, suggest close association of the metabolism of methylated phospholipids with chemotaxis in rabbit peritoneal leukocytes.

Animals↗
PubMed1978

Chemotactic antibody.

Antibody of the immunoglobulin G class to herpes simplex virus and antibody of the immunoglobulin M class to sheep red blood cells were coupled to the synthetic peptide formylmethionylleucylphenylalanine (fMet-Leu-Phe), which is chemotactic for both mononuclear and polymorphonuclear leukocytes. The resulting molecules were chemotactic and retained their antigen-binding activity. When antibodies coupled to fMet-Leu-Phe were incubated with antigen, the resulting immune complexes were also chemotactic. Chemotactic antibody may provide a potent means of enhancing the migration of inflammatory cells to specific sites.

Antibodies↗
PubMed1978

Role of secretory events in modulating human neutrophil chemotaxis.

The relationship between neutrophil polymorphonuclear leukocyte (PMN) locomotion and the exocytosis of neutrophil cytoplasmic granules was studied by assessing these processes in cells migrating through micropore filters and by measuring the effects of degranulating stimuli on PMN chemotaxis, orientation, adhesiveness, and ability to bind the chemoattractant f-Met-Leu-[3H]Phe. Studies of cells migrating through cellulose nitrate filters indicated that concentrations of f-Met-Leu-Phe optimal for exocytosis were greater than those optimal for chemotaxis and actually inhibited cell migration. In other studies incubation of PMNs with concentrations of secretagogues causing exocytosis of 30% or greater PMN lysozyme increased cell adhesiveness and inhibited chemotaxis. PMNs that had secreted more than 30% lysozyme appeared round, did not orient in a gradient of chemoattractant, and were capable of significantly less f-Met-Leu-[3H]Phe binding than were control cells. The decreased binding of f-Met-Leu-Phe was not associated with hydrolysis of chemotactic peptide by washed cells, although peptide hydrolysis was caused by cell products secreted extracellularly after vigorous exocytosis. In contrast, when only 10--15% cellular lysozyme was released f-Met-Leu-Phe binding was enhanced significantly and there was no depression of chemotaxis. The data indicate limited exocytosis of intracellular granule contents is associated with increased availability of PMN cehmotactic factor receptors. Vigorous exocytosis is associated with inactivation of chemotactic responsiveness related to increase cell adhesiveness, decreased PMN binding of chemotactic factors, and to hydrolysis of chemoattractants by factors secreted extracellularly.

Binding Sites↗
PubMed1976

The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils.

24 di-, tri-, and tetrapeptides have been synthesized as a start of a systematic study of the structural requirements for chemotactic activity and lysosomal enzyme-releasing ability in rabbit neutrophils. All but two of them are N-formyl methionyl peptides. Using the method of Zigmond and Hirsch (10), two representative peptides, F-Met-Leu-Phe and F-Met-Met-Met, were shown to stimulate directed, as well as, random locomotion; thus, they were truly chemotactic. The various peptides showed a wide spread in activity. F-Met-Leu-Phe, the most active peptide studied, had an ED50 for induced migration of 7 X 10(-11) M and for lysozyme and beta-glucuronidase release of 2.4 X 10(-10) M and 2.6 X 10(-10) M, respectively; the least active, Met-Leu-Glu was 26 million times less active in these respects. The relation of activity to structure is exceedingly specific, very small changes in structure making large changes in activity. Moreover, this specificity exhibits a definite regularity and pattern; the activity of a given peptide depends not only on its constituent amino acids but on the position of the amino acid in the peptide chain. Most striking in this last regards is the high activity conferred by phenylalanine when it is in the carboxyl terminal position of a tripeptide, whereas, as the second amino acid from the NH2 terminal end whether in a tripeptide or a dipeptide, it contributes no more to the activity than other amino acids with hydrophobic side chains such as leucine or methionine. The high activity and the specificity and nature of the structural requirements strongly suggest that the primary interaction of peptide and neutrophil leading to either chemotaxis or lysosomal enzyme release is a binding of the peptide with a stereospecific receptor on the neutrophil surface. Whether all chemotactic factors act through the same receptor is not known. An essentially exact correlation exists between the concentrations of the various synthetic peptides required to induce migration and their ability to induce release of lysozyme or beta-glucuronidase. This implies that these two neutrophil functions are triggered by teh same primary interaction; possibly, the binding of the peptides to the same putative receptor. A higher concentration of a given peptide is required to stimulate lysosomal enzyme release than a corresponding migratory response. A slightly but significantly higher concentration of peptide is required to induce beta-glucuronidase secretion than lysozyme release.

Animals↗
PubMed1976

Role of a peptidase in phagocyte chemotaxis.

The potencies of N-formylmethionyl (fMet) peptides as chemotactic agents for phagocytes are related to the rates at which they are hydrolyzed. Furthermore, chloromethyl ketones inhibit chemotaxis as do the products of hydrolysis of fMet peptides. The directed migration of cells in response to such peptides is probably brought about by the binding of the peptide to a cell receptor with subsequent cleavage by peptidase specific for aromatic residues, a process that allows the chemical gradient to be detected.

Animals↗
PubMed1976

Histamine release by chemotactic, formyl methionine-containing peptides.

Certain formyl dipeptides and tripeptides containing methionine released histamine from human basophils at concentrations of 10(-4) to 10(-7) M. However, N-formyl amino acids did not release histamine. Tripeptides, in general, were more active than dipeptides. An acyl group was required for histamine release although an N-terminal position for Met was not essential. Histamine release from human basophils by these peptides correlated well with their chemotactic activity for rabbit leukocytes.

Animals↗
PubMed1975

N-formylmethionyl peptides as chemoattractants for leucocytes.

Leucocytes such as neutrophils are attracted by N-formylmethionine, but not by methionine. Di- and tripeptides containing formylmethionine are strong attractants for both neutrophils and macrophages, whereas the corresponding nonacylated compounds are not chemotactic. The formylated peptides may be related to an incompletely characterized chemotactic material normally produced by bacteria which attract the same animal cells.

Chemotaxis↗
PubMed1975

The isolation and partial characterization of neutrophil chemotactic factors from Escherichia coli.

Heat-stable, chemotactically active peptides have been obtained from Escherichia coli culture filtrates. They range in size between 150 and 1500 daltons and are anionic at neutral pH. Free carboxyl groups but not free amino groups appear to be required for activity. The N-terminal group may be blocked. There do not appear to be internal aromatic or basic residues in the chemotactically active fractions. A highly purified, not completely characterized, fraction was found to contain aspartic acid, serine, glutamic acid, alanine, and glycine.

Acetylation↗