Biomedical subjects

I Spilberg

Publications and source records attributed to I Spilberg.

At least 55 records · Page 3Linked to original sources

PubMed1979

Chemotactic factor-induced generation of superoxide radicals by human neutrophils: evidence for the role of sodium.

The role of sodium ion in superoxide (O2-) generation by human peripheral neutrophils was investigated. Cells were activated by exposure to the synthetic tripeptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), and O2- release was assessed by ferricytochrome c reduction after 5 min of incubation at 37 degrees C in the presence of FMLP 4 X 10(-8) M. In the absence of monovalent cations (isotonic glucose), negligible O2- generation occurred. There was a progressive increase in the magnitude of FMLP-induced O2- generation with increasing Na+ concentration up to 90 mM, where the response was noted to plateau. Varying the K+ concentration (1 to 10 mM) had no effect on the amount of O2- produced in the presence of Na+ 140 mM. FMLP also stimulated 22Na+ and 48Ca2+ uptake by the cells in a dose- and time-dependent fashion. FMLP-induced 22Na+ uptake appeared to be independent of the external Ca2+ concentration ( to 4 mM). In contrast, there was a progressive decrease in themagnitude of the FMLP-induced increase in 45Ca2+ uptake as the Na+ concentration was reduced by replacement with choline+ or glucose. These studies support a requirement for Na+ in FMLP-induced O2- generation and suggest that a Na+ influx may underlie the nature of this requirement. The data are also consistent with the hypothesis that a Na+ influx may precede the Ca2+ influx in the FMLP-induced activation sequence.

Binding Sites↗

PubMed1979

A proposed model for chemotactic deactivation: evidence for microtubule modulation of polymorphonuclear leukocyte chemotaxis.

Incubation of the CFs Gly-His-Glyc or CCF with PMNs in the absence of a gradient, resulted in a dose-dependent depression in chemotactic activity when, after washing, the cells were challenged with the CFs in a Boyden chamber. When the cells were preincubated with either CF and suitable concentrations of colchicine, the inhibition of chemotaxis that either of these agents induced when incubated with the cells alone was abolished. Deactivation reappeared when the optimal ratio between colchicine and CF was altered in either direction. Ultramicroscopic studies showed an increase in centriole-associated microtubules following incubation of cells with CFs. This increase was arrested by prior exposure of the cells to colchicine. Colchicine did not alter the specific binding of CCF to human neutrophils, and lumicolchicine had no effect on either chemotaxis or deactivation. Our data suggest that the control of PMN chemotaxis is predicted upon microtubule assembly evoked by cell interaction with a chemotactic gradient. Chemotaxis would be prevented by conditions that inappropriately organize responsive microtubules in either a polymerized or depolymerized configuration.

Chemotaxis↗

PubMed1978

Dissociation of the neutrophill functions of exocytosis and chemotaxis.

The peptide Gly-His-Gly is shown to be chemotactic for human neutrophils in vitro and for rabbit neutrophils in vivo but to be unable to induce lysosomal enzyme release from human neutrophils at sublytic concentrations. The failure of this chemotactic peptide to elicit lysosomal enzyme release provides evidence that interactions with a chemotactic receptor does not necessarily activate chemotaxis and exocytosis in the human neutrophil, thus suggesting that the presumed common pathway of exocytosis and chemotaxis may be divergent at the cell receptor and/or postreceptor level.

Albumins↗

PubMed1977

A mechanism of action for non-steroidal anti-inflammatory agents in calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis.

The acute inflammatory response to calcium pyrophosphate dihydrate crystals follows the meeting of neutrophils and crystals. The ensuing phagocytosis leads to the generation of a glycoprotein chemotactically active for neutrophils and to the release of lysosomal enzymes. Indomethacin and phenylbutazone, at therapeutic concentrations, impaired phagocytosis of the crystals and generation of chemotactic factor activity. Colchicine had no effect upon phagocytosis but significantly impaired the appearance of chemotactic factor activity.

Arthritis↗

PubMed1977

Induction of arthritis by purified cell-derived chemotactic factor: role of chemotaxis and vascular permeability.

The injection of monosidium urate-induced chemotactic factor into the joint cavities of rabbits induces an acute inflammatory response that resembles the one produced by monosodium urate crystals. The leukocyte accumulation induced by the factor was not accompanied by a measurable increase in vascular permeability as measured by appearance of 125I-albumin in the joint cavity. When histamine was injected into the joints, a marked increase in vascular permeability but no leukocytosis above control levels was observed. The above results suggest that the cell-derived factor is primarily responsible for the accumulation of cells seen in the acute inflammation induced by monosodium urate crystals.

Animals↗

PubMed1977

Calcium pyrophosphate dihydrate (CPPD) crystal-induced chemotactic factor: subcellular localization, role of protein synthesis and phagocytosis.

A factor with chemotactic properties for polymorphonuclear leukocytes appears in their lysosomal fraction following phagocytosis of CCPD crystals. The factor, whose appearance was blocked by inhibition of protein synthesis, was estimated to have a molecular weight of 8,400 daltons. Inhibition of crystal phagocytosis by cytochalasin B was also shown to inhibit the generation of chemotactic factor activity, indicating that ingestion of the crystals by the cell is essential for the generation of the CPPD crystal-induced chemotactic factor. This latter finding provides a clue in the understanding of the development and termination of the acute pseudogout attack.

Calcium Pyrophosphate↗

PubMed1977

Inhibition of polymorphonuclear leukocyte capping by a chemotactic factor.

Incubation of human polymorphonuclear leukocytes with colchicine and fluorescein-concanavalin A leads to the formation of a polarized cap of fluorescence not seen if cells are incubated with fluorescein-Con A along. When cells are preincubated with a chemotactic factor before colchicine treatment, the capping is inhibited in a dose-related manner. Studies with alpha-methylmannoside indicate that the caps represent extracellular fluorescein-Con A and are not areas of Con A internalization. Experiments utilizing an irreversible inhibitor of serine esterases suggest that a chemotactic factor-activated enzyme is involved in the inhibition of cap formation in the human neutrophil.

Cell Membrane↗

PubMed1976

The roles of renal catabolism and uremia in modifying the clearance of fibrinogen and its degradative fragments D and E.

Elevated levels of fibrinogen/fibrin degradation products (FDP) occur in uremia, and have been thought to be in part related to intravascular coagulation in the kidney. More recent data indicated that delayed catabolism of fibrinogen fragment D occurred in anephric animals. To further evaluate FDP catabolism in the kidney, turnover studies of purified dog 131I-Fg-D and 125I-Fg-E were performed on dogs before and after acute subtotal nephrectomies, and later during chronic uremia. 131I-fibrinogen clearances were also perfomed. Slowed catabolism of Fg-D and Fg-E was observed in both the acute and chronic uremic stages. Altered urinary excretion was not a factor as only minimal amounts of Fg-D and Fg-E were excreted in the urine of the control animals. In the 131I-fibrinogen studies, there were significant changes in plasma volume, fibrinogen t 1/2, and intravascular/extravascular distribution, but not in fractional catabolic rate. To differentiate fully, the effects of uremia from those of loss of catabolic renal tissue, the Fg-D and Fg-E turnover studies were repeated on other animals with intact kidneys whose ureters were diverted into the peritoneum and compared to subsequent studies after total nephrectomy. The control and ureter-severed studies had the same clearance pattern, whereas decreased catabolism occurred in the nephrectomized dogs. The results demonstrate uremia per se does not have a major effect upon the catabolism of fibrinogen, Fg-D, and Fg-E. Loss of renal tissue does impair the clearance of Fg-D and Fg-E, indicating these proteins are normally catabolized in part by the kidneys. Thus elevated plasma FRA in uremic patients may reflect decreased Fg-D and Fg-E catabolism rather than increased FDP production from primary or secondary fibrinolysis.

Animals↗

PubMed1975

Studies on crystal-induced chemotactic factor. II. Role of phagocytosis.

The interaction of polymorphonuclear leukocytes (PMN's) and urate crystal leads to the formation of a chemotactic factor. The purpose of this study was to determine the need for ingestion of crystals by the cells in the generation of the chemotactic factor. Our studies showed that when PMN's were incubated with cytochalasin B, an inhibitor of phagocytosis, and urate crystals, no chemotactic activity appeared in the lysosomal extract of the cells. Likewise, no chemotactic activity was present in the media of PMN's incubated with crystals although lysosomal enzyme activity was increased. These findings indicate that phagocytosis is required for chemotactic activity to appear. Our studies also show that cytochalasin B increases the release of lysosomal enzyme B-glucuronidase but not of cytoplasmic enzyme lactic dehydrogenase from PMN's when the cell encounters urate crystals.

Animals↗

PubMed1975

A mechanism for decreased resistance to infection by gram-negative organisms during acute alcoholic intoxication.

The propensity of alcoholics to develop infections with gram-negative bacteria is well known. However, the known effects of ethanol on host-defense mechanisms do not explain this tendency satisfactorily. Since the principal defense mechanism against gram-negative bacteria is their destruction by complement in the presence of specific antibody, we investigated the effect of acute ethanol intoxication on serum complement concentrations and correlated these with serum bactericidal activity against a gram-negative organism. Serial measurements of total hemolytic complement (CH5O) and C'3, ethanol concentration, and serum bactericidal capacity were performed on the serum of 7 dogs infused with a 10 per cent ethanol solution. All animals showed a substantial decrease in total hemolytic complement activity which was inversely related to the increase in serum ethanol concentration. A decrease in serum bactericidal activity correlated with the decrease in CH50. Control animals showed no variation in either CH50 or serum bactericidal activity. Immunoprecipitation studies, using antibody to dog C'3, indicated that serum concentrations of this protein were not altered by infusing the animals with ethanol. Incubation of serum in vitro with both ethanol and acetaldehyde had no effect on CH50. We conclude that the effect of ethanol on serum complement is an in vivo phenomenon probably relating to decrease in the synthesis of one or more of the components of complement other than C'3, although the formation of an anticomplementary substance cannot be excluded. These findings are presented as a possible explanation for the development of infections with gram-negative bacteria in ethanol-intoxicated subjects.

Acetaldehyde↗

PubMed1974