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M Columbo

Publications and source records attributed to M Columbo.

31 records · Page 2Linked to original sources
PubMed1986

Forskolin inhibits the release of histamine from human basophils and mast cells.

We found that forskolin (10(-7) to 3 X 10(-5) M) caused dose-related inhibition of antigen-induced histamine release from human basophil leukocytes. The dose-response inhibition curve was paralleled by a forskolin-induced increase in cyclic AMP (cAMP) levels in human leukocyte preparations. The kinetics of inhibition of histamine release and of the increase in leukocyte cAMP were the same. In a second series of experiments we evaluated the effect of forskolin on antigen-induced histamine release from chopped human lung passively sensitized with serum from an allergic patient. Forskolin (10(-7) to 3 X 10(-5) M) dose-dependently inhibited the release of histamine from human lung mast cells. Thus forskolin appears to modulate the release of mediators of the immediate hypersensitivity reaction, presumably through activation of adenylate cyclase in human basophils and mast cells.

Adult↗
PubMed1986

Modulation of the release of histamine and arachidonic acid metabolites from human basophils and mast cells by auranofin.

In these experiments the effects of pharmacological concentrations of auranofin, a new absorbable gold compound, were assessed on the release of histamine and peptide leukotriene C4 (LTC4) from human basophils and lung mast cells. Auranofin, at pharmacological concentrations, inhibited in vitro histamine and LTC4 release from human basophils induced by anti-IgE. Inhibition began at about 3 X 10(-7) M and was maximum at 10(-5) M. We also evaluated the effect of auranofin on the release of histamine and LTC4 induced by anti-IgE from mast cells purified from human lung. Auranofin (3 X 10(-7) to 10(-5) M) dose-dependently inhibited the release of histamine and LTC4 from human lung mast cells. Thus pharmacological concentrations of auranofin cause dose-related inhibition of histamine release and de novo synthesis of LTC4 by human basophils and lung mast cells.

Adult↗
PubMed1986

Physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells.

We have previously shown that physiological concentrations of zinc (congruent to 7 X 10(-6) M) inhibit the release of histamine from human basophil leukocytes (Marone et al., J. Pharmacol. Exp. Ther. 217: 292, 1981). In these experiments we compared the effect of zinc chloride on the release of chemical mediators from human basophils and mast cells isolated from human lung. Preincubation (5 min, 37 degrees C) of human basophils and lung mast cells with zinc chloride (10(-6)-3 X 10(-5) M) caused dose-related inhibition of histamine and peptide leukotriene C4 (LTC4) release induced by anti-IgE. Increase Ca2+ concentrations (0.3 to 6 mM) in the extracellular medium completely reversed the inhibitory effect of zinc on anti-IgE-mediated histamine secretion. Zinc chloride was a competitive antagonist of the action of Ca2+ in histamine secretion induced by anti-IgE with a dissociation constant (Kd) of about 10(-5) M in both the basophil and mast cell systems. Thus physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells, presumably by blocking Ca2+ uptake induced by anti-IgE activation.

Basophils↗
PubMed1985

Histamine release from human basophils by pepstatin A.

Pepstatin A, a pentapeptide isolated from cultures of actinomycetes, induced histamine secretion from human basophils in the concentration range of 3 X 10(-7) to 10(-4) M. The characteristics of this reaction were similar to those of f-met-peptide-induced histamine release: pepstatin A-induced release required Ca2+ and the release reaction was complete within 2 min at 22 or 37 degrees C, but did not occur at 4 degrees C. Release by both pepstatin A and f-met-peptide was reversibly inhibited by two non-releasing analogs of f-met-peptide, CBZ-Phe-Met and BOC-Met-Leu-Phe. Further, there was complete cross-desensitization between pepstatin A and f-met-peptide, while cells desensitized to pepstatin A released normally with anti-IgE and vice versa. A variety of pharmacological agents had similar effects on both pepstatin A and f-met-peptide-induced release (e.g., no enhancement with D2O; marked enhancement with cytochalasin B). We suggest that pepstatin A induces histamine release from human basophils by activating a cell surface receptor(s), also activated by the synthetic tripeptide f-met-peptide.

Basophils↗
PubMed1985

Activation of human basophils by bacterial products.

Staphylococcus aureus Cowan I (Cowan Staph A+), which synthesizes protein A (Staph A), induced histamine release from human basophils. In contrast, S. aureus Wood 46 (Wood Staph A-), which does not synthetize Staph A, did not induce histamine secretion. Soluble Staph A and Cowan Staph A+ induced histamine release by interacting with the alternative F(ab')2-binding site of IgE and/or IgG present on human basophils. Pepstatin A, a pentapeptide synthetized by various actinomycetes, induced histamine secretion by activating a specific membrane receptor, which is also activated by synthetic formylmethionine-containing peptides.

Basophils↗
PubMed1984

The mechanism of basophil histamine release induced by pepstatin A.

Pepstatin A, a natural pentapeptide isolated from cultures of actinomycetes, induced histamine secretion from human basophils in the concentration range of 3 X 10(-7) to 10(-4) M. The characteristics of this reaction were similar to those of f-met-peptide-induced histamine release: pepstatin A-induced release required Ca2+, and the release reaction was complete within 2 min at 22 or 37 degrees C but did not occur at 4 degrees C. There was excellent correlation (r = 0.93; p less than 0.001) between the maximal histamine release induced by pepstatin A and f-met-peptide, but there was no relationship to the capacity of basophils to release with anti-IgE (r = -0.03) or the Ca2+ ionophore A23187 (r = -0.22). Release by pepstatin A was reversibly inhibited by two nonreleasing analogs of f-met-peptide, CBZ-Phe-Met and BOC-Met-Leu-Phe. BOC-Met-Leu-Phe competitively inhibited the effect of both f-met-peptide and pepstatin A on histamine release from basophils. The dissociation constant (Kd) for the BOC-Met-Leu-Phe-receptor complex in both conditions was approximately 10(-6) M. Furthermore, there was complete cross-desensitization between pepstatin A and f-met-peptide, whereas cells desensitized to pepstatin A released normally with anti-IgE and vice versa. A variety of pharmacologic agents had similar effects on both pepstatin A- and f-met-peptide-induced release (e.g., slight inhibition with cyclic AMP-active agents, no enhancement with D2O, and marked enhancement with cytochalasin B). We suggest that the natural pentapeptide pepstatin A induces histamine release from human basophils by activating a cell surface receptor(s) also activated by the synthetic tripeptide f-met-peptide.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Possible role of calmodulin in the control of lysosomal enzyme release from human polymorphonuclear leukocytes.

Human polymorphonuclear leukocytes (PMNs) were found to contain a mean +/- S.E.M. of 21.7 +/- 7.9 ng of immunoreactive calmodulin (CaM)/10(6) PMNs, which represents 0.032 +/- 0.001% of the total cellular protein. The functional role of CaM in the control of lysosomal enzyme release from human PMNs was investigated using several CaM antagonists. Trifluoperazine (TFP) (10(-6)-2 X 10(-5) M), pimozide (10(-6)-1.5 X 10(-5) M), chlorpromazine (CPZ) (10(-5)-10(-4) M) and promethazine (2 X 10(-5)-10(-4) M) inhibited in vitro lysosomal enzyme release from human PMNs induced by immunological (serum-treated zymosan, concanavalin A and formyl-L-methionyl-L-leucyl-L-phenylalanine) and nonimmunological (Ca++ ionophore A23187) stimuli. Trifluoperazine sulfoxide (TFP-S) and chlorpromazine sulfoxide (CPZ-S), which have very low affinity for CaM, had practically no inhibitory effect on lysosomal enzyme release. The inhibitory effect of TFP could be made irreversible by irradiating the cells with UV light. A sulfonamide derivative, W-7, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (10(-5)-2 X 10(-4) M), which selectively binds to CaM, inhibited the release of lysosomal enzymes from PMNs. In contrast, the chloride-deficient analog, W-5, N-(6-aminohexyl)-1-naphthalenesulfonamide hydrochloride, which interacts only weakly with CaM, had practically no inhibiting effect. The IC50 for enzyme release by a series of eight CaM antagonists was closely correlated (r = 0.89; P less than .001) with their affinity for binding to CaM, supporting the concept that these agents act by binding to CaM and thereby inhibiting lysosomal enzyme release.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1983

Inhibition of histamine release from human basophils in vitro by calmodulin antagonists.

Calmodulin is a ubiquitous and versatile Ca2+-binding protein that plays a pivoting role in cellular metabolism. We have investigated the possibility that calmodulin plays a role in immediate hypersensitivity reactions by evaluating the effects of two agents, trifluoperazine dihydrochloride (TFP) and the sulfonamide derivative N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) which selectively bind to calmodulin. TFP and W-7 cause a dose-dependent inhibition of histamine secretion from human basophils in vitro induced by several immunological (i.e., antigen and anti-IgE) and nonimmunological (i.e., formyl-methionine-containing peptide and the Ca2+ ionophore A23187) stimuli. These results indicating that two specific calmodulin antagonists are potent inhibitors of the secretory response of human basophils support the hypothesis that calmodulin may play a role in the control of the release of preformed mediators from human inflammatory cells.

Adult↗
PubMed1983

Immunofluorescence localization of calmodulin in human polymorphonuclear leukocytes.

Human polymorphonuclear leukocytes (PMNs) were purified (approximately equal to 99%) from peripheral blood of normal, adult volunteers. The indirect immunofluorescence technique was used to investigate the presence and the localization of calmodulin in human PMNs. The cellular distribution of calmodulin has been evaluated using an affinity chromatography-purified sheep IgG anti-calmodulin and fluorescein-conjugated rabbit anti-sheep IgG. The anti-calmodulin immunofluorescence pattern suggests that calmodulin is evenly distributed throughout the cytoplasm of human PMNs.

Adult↗
PubMedDate not supplied

The releasability of lysosomal enzymes from neutrophil leukocytes in patients with rheumatoid arthritis.

OBJECTIVE: To study the enzyme content and the "releasability" of lysosomal enzymes (lysozyme and beta-glucuronidase) in neutrophils purified from peripheral blood of patients with rheumatoid arthritis (RA) or normal subjects. METHODS: Neutrophils were obtained from 13 patients (10 women and 3 men) with rheumatoid arthritis and from 11 healthy subjects (8 women and 3 men). We measured: (1) lysosomal enzyme (lysozyme and beta-glucuronidase) content; (2) spontaneous enzyme release; (3) lysosomal enzyme release after cell challenge with different segretagogues (FMLP, C5a, aggregated IgG, zymosan and Ca2+ ionophore A23187). RESULTS: The lysosomal enzyme content was not statistically different in control subjects and in patients with RA (7.4 +/- 1.9 vs 6.3 +/- 0.8 micrograms/10(6) neutrophils for lysozyme; 102.9 +/- 16.4 vs 78.9 +/- 11.2 micrograms/10(6) neutrophils for beta-glucuronidase in control and RA subjects, respectively, p = NS). Unstimulated release of lysozyme was significantly lower in RA patients (3.8 +/- 1.1%) when compared to control subjects (9.5 +/- 2.1%) (p < 0.05). In contrast, spontaneous release of beta-glucuronidase did not differ in the two groups (5.5 +/- 0.9% and 3.8 +/- 1.1% in control and RA subjects, respectively). Enzyme release induced by FMLP (3 x 10(-9)-3 x 10(-7) M), C5a (10(-8)-10(-7) M), aggregated IgG (0.1-0.6 mg/ml), or Ca2+ ionophore A23187 (0.1-1 microgram/ml) did not differ statistically in the two groups of subjects. Neutrophil stimulation by serum-treated zymosan, at the concentration of 0.3 mg/ml, induced a release of lysozyme that was significantly higher in patients with RA when compared to control subjects (p < 0.05), whereas zymosan-activated beta-glucuronidase secretion was similar in the two donor populations. CONCLUSIONS: This study suggests that the contribution of leukocytes to the inflammatory processes typical of RA does not depend on an altered "releasability" of preformed mediators from peripheral blood neutrophils.

Adult↗