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J C Fantone

Publications and source records attributed to J C Fantone.

At least 73 records · Page 4Linked to original sources
PubMed1984

Prostaglandin modulation of N-formylmethionylleucylphenylalanine-induced transmembrane potential changes in rat neutrophils.

Prostaglandins of the E-series (PGEs) and PGI2 will inhibit formylmethionylleucylphenylalanine-(f-Met-Leu-Phe) induced lysosomal enzyme release and superoxide-anion (O2-) production by neutrophils. The inhibitory effects of PGEs and PGI2 on neutrophil functional responses have been correlated with their ability to increase intracellular cAMP. In this study we have examined the effects of PGEs and PGI2 on f-Met-Leu-Phe- and phorbol-myristate-acetate-induced rat neutrophil membrane potential changes using an optical probe of membrane potential 3,3-dipropylthiodicarbocyanine iodide. 15-(S)-15-methyl-PGE1 (15-methyl-PGE1), a stable analogue of PGE1 and PGI2 inhibited f-Met-Leu-Phe-induced transmembrane potential changes in a dose-dependent manner. This inhibition was correlated with the ability of these agents to increase intracellular cAMP levels and inhibit O2- production and degranulation. In contrast, 15-methyl-PGE1 and PGI2, did not inhibit phorbol-myristate-acetate-induced transmembrane potential changes and O2- production. These results suggest independent mechanisms of activation of neutrophils by phorbol myristate acetate and f-Met-Leu-Phe, and they also suggest that the inhibitory effects of prostaglandins and cAMP on f-Met-Leu-Phe-stimulated cells is at a step or steps prior to activation of those processes involved in effecting changes in transmembrane potential, which are common to both stimuli.

Alprostadil↗
PubMed1984

Functional responses of tumor cells to phorbol esters: role for prostaglandins.

The effects of phorbol esters on five murine cell lines were examined. In three of these lines, all of which were highly malignant, phorbol ester treatment induced motility and foreign surface adherence while concomitantly inhibiting proliferation. In two other, nonmalignant cell lines phorbol ester treatment stimulated proliferation but did not influence motility or adherence. Possible roles for prostaglandins in these responses were investigated. The mitogenic effects of the phorbol esters were duplicated by prostaglandin F2 alpha. In contrast, prostaglandin E1 and prostacyclin inhibited proliferation induced by the phorbol esters. These agents also inhibited phorbol ester-induced cell motility.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Inhibition of bleomycin-induced pulmonary fibrosis by lipopolysaccharide.

Current evidence suggests that bleomycin toxicity may be attributable to its DNA degradative activity possibly via generation of free radicals and O2 metabolites as mediators. Since lipopolysaccharide (LPS) has been known to provide protection against O2 toxicity, which is correlated with increased activity of O2 metabolite-detoxifying enzymes, the effect of this agent on bleomycin-induced pulmonary fibrosis was examined. Endotracheal bleomycin administration caused increased lung collagen synthesis. A single intraperitoneal injection of LPS (500 micrograms/kg) at day zero significantly decreased these increases. Total bleomycin-induced lung collagen increase was also significantly reduced. LPS alone had no significant effect on total lung catalase activity. Glutathiione peroxidase activity, however, was significantly decreased by 15.8% compared to untreated animals at 2 days after LPS treatment and remained unchanged at other time points. In addition, superoxide dismutase activity was significantly elevated by 30% above untreated animals only at 14 days after LPS administration and remained unchanged at other time points. Endotracheal bleomycin administration alone caused significant reductions in catalase activity at 2 days and 2 weeks after treatment, whereas glutathione peroxidase activity increased above control untreated animals at 2 and 4 weeks, respectively. Superoxide dismutase activity was unaffected by bleomycin treatment. Pretreatment with LPS before bleomycin prevented these reductions or caused increases in the activities of these enzymes at 2 days. Glutathione peroxidase was increased and was significantly greater than those animals treated with bleomycin alone. Catalase also was higher in the LPS plus bleomycin group (by 22.2%, p less than 0.05) than the bleomycin group alone. Compared to the effects on lung collagen synthesis and content, LPS treatment resulted in much less dramatic changes in total lung antioxidant enzyme activities. This discrepancy between the intensity of LPS effects on lung O2 metabolite-detoxifying enzymes and that on pulmonary fibrosis implies that the LPS-ameliorating effect on pulmonary fibrosis could not be totally explained by increased ability to detoxify O2 metabolites. Rather, the data would favor the possibility that LPS inhibits bleomycin-induced pulmonary fibrosis either by its known immunosuppressive effects or some other unknown mechanism. The former would be in agreement with previous data which suggest that an intact immune response is necessary for complete expression of the fibrogenic response to bleomycin.

Animals↗
PubMed1984

Potentiation of alpha-naphthyl thiourea-induced lung injury by prostaglandin E1 and platelet depletion.

alpha-Naphthyl thiourea ( ANTU ) produces pulmonary endothelial injury, pulmonary edema, and pleural effusions in rats in a dose-dependent manner. Since prostaglandins of the E series have been shown to modulate inflammatory responses in vivo and neutrophil and platelet function in vitro we investigated the effects of prostaglandin E1 (PGE1) on ANTU -induced lung injury. Systemic administration of 15-(S)-15-methyl-PGE1 (15-M-PGE1), a stable analog of PGE1, potentiated lung injury induced by ANTU in a dose- and time-dependent manner. 15-M-PGE1 (1 mg/kg, subcutaneously) administered 1 hour prior to ANTU treatment (1 mg/kg, intraperitoneally) resulted in a 164% increase (p less than 0.001) in pleural effusion formation and a 42% increase (p less than 0.02) in wet lung weight at 4 hours after ANTU administration. This was associated with increased pulmonary endothelial cell blebbing and gap formation with a decrease in the number of platelet thrombi in 15-M-PGE1-treated animals compared with controls. 15-(S)-15-methyl-prostaglandin F2 alpha, was less effective than 15-M-PGE1 in potentiating ANTU -induced lung injury. Platelet depletion, but not neutrophil depletion, also potentiated ANTU -induced lung injury, suggesting a protective role for platelets. Platelets isolated from 15-M-PGE1-treated animals demonstrated an approximately 50% decreased aggregation response to adenosine diphosphate. 15-M-PGE1 (1 mg/kg) treatment combined with platelet depletion resulted in a 1.7-fold increase (p less than 0.01) in pleural effusions in ANTU -treated (1 mg/kg) animals compared with platelet depletion alone. These studies indicate that systemic treatment of rats with 15-M-PGE1 will potentiate ANTU -induced lung injury. This injury may be in part secondary to the ability of 15-M-PGE1 to inhibit platelet function. However, platelet depletion studies suggest that 15-M-PGE1 has additional effects, possibly on endothelial cells and/or vascular smooth muscle cells that contribute to the potentiation of ANTU -induced lung injury.

Alprostadil↗
PubMed1984

Stimulus specificity of prostaglandin inhibition of rabbit polymorphonuclear leukocyte lysosomal enzyme release and superoxide anion production.

Prostaglandins (PGs) of the E series and PGI2 have been shown to inhibit acute inflammatory reactions in vivo and polymorphonuclear leukocyte (PMN), chemotaxis, lysosomal enzyme release, and superoxide anion (O-2) production in vitro. This inhibition of neutrophil stimulation by PGEs and PGI2 has been correlated with their ability to increase intracellular cyclic adenosine monophosphate (cAMP) levels. However, the mechanism(s) by which PGEs and PGI2 alter the complex biochemical and biophysical events associated with stimulus-response coupling in the neutrophil are not clear. It is reported here that both PGEs and PGI2 in micromolar concentrations inhibit formyl-methionyl-leucyl-phenylalanine (FMLP)- and zymosan-induced lysosomal enzyme secretion and superoxide anion production in a dose-dependent manner. No preincubation time of PMNs with the prostaglandins is required for inhibition. Addition of PGEs 10 seconds or later after FMLP stimulation does not alter the biologic response of the neutrophils to the stimulus, suggesting that the prostaglandin inhibition effects early events associated with stimulus-response coupling in the neutrophil. Prostaglandin inhibition of lysosomal enzyme release by the calcium ionophore A23187 was overcome by increasing the extracellular ionophore and/or calcium concentration, suggesting that PGs may modulate intracellular free calcium levels in a manner similar to that observed with platelets. Inhibition of phorbol myristate acetate (PMA)-induced neutrophil lysosomal enzyme secretion by PGEs and PGI2 was overcome by increasing concentrations of PMA. However, neither PGEs nor PGI2 altered O-2 production by PMA-treated neutrophils. These data indicate a dissociation between PMA-stimulated O-2 production and lysosomal enzyme release. These findings are consistent with the hypothesis that inhibition of neutrophil stimulation by PGEs and PGI2 is a result of increased intracellular cyclic AMP levels and modulation of calcium-dependent events. In addition, the data indicate that there are at least two mechanisms by which PMNs can be stimulated to produce O-2, one inhibited by PGEs and PGI2 and a second independent of prostaglandin modulation.

Acetylglucosaminidase↗
PubMed1983

Prostaglandin E1 and prostaglandin I2 modulation of superoxide production by human neutrophils.

15(S)-15-methyl-prostaglandin E1 and prostaglandin I2 rapidly and reversibly inhibit formyl-methionyl-leucyl-phenylalanine induced superoxide production by human neutrophils. In contrast, 15(S)-15-methyl-prostaglandin E1 and prostaglandin I2 did not alter the rate or the total amount of superoxide production by human neutrophils stimulated with either phorbol myristate acetate or arachidonic acid. These data suggest that the production of superoxide anion by human neutrophils may be mediated by at least two mechanisms, one regulated by prostaglandins and intracellular cyclic adenosine monophosphate levels and a second independent of prostaglandin modulation.

Alprostadil↗
PubMed1983

Modulation of tumor cell adherence by prostaglandins.

The initiation of tumor cell metastasis is thought to involve the adherence of circulating tumor cells to endothelial cells and/or basement membranes. The adherence of Walker carcinosarcoma tumor cells to foreign surfaces induced by phorbol myristate acetate and the chemotactic formyl peptide, formylmethionyl-leucyl-phenylalanine is inhibited by prostacyclin and 15-S-15-methyl PGE1 in a dose-dependent manner. The inhibition of tumor cell adherence by prostacyclin and 15-S-15-methyl PGE1 is associated with a 3- to 5-fold increase in intracellular cyclic adenosine monophosphate (cAMP) concentrations. The data suggests that the local production of prostaglandins may be an important modulator of tumor cell metastasis due to its direct effect on the tumor cells.

Animals↗
PubMed1983

Anti-inflammatory effects of prostaglandin E1: in vivo modulation of the formyl peptide chemotactic receptor on the rat neutrophil.

The local generation of chemotactic factors at sites of acute inflammation is thought to be responsible for the recruitment of polymorphonuclear leukocytes (PMN) from the intravascular compartment to the site of tissue injury (1). Many of these potent phlogistic mediators have also been shown to activate PMN resulting in degranulation of lysosomal granules with release of hydrolytic enzymes into the extracellular environment and the generation of superoxide anion (O2-) and other toxic metabolites (reviewed in Reference 2). Several in vitro studies have shown that treatment of PMN with specific prostaglandins will inhibit both soluble mediator- and particulate material-induced neutrophil lysosomal enzyme release and chemotaxis (3, 4). In vivo studies have demonstrated potent anti-inflammatory activity of prostaglandins of the E series (5-7). Systemic administration of prostaglandin E1 (PGE1) or its stable analog 15-(S)-15-methyl-PGE1 (15-M-PGE1) will inhibit neutrophil dependent immune complex tissue injury in a dose-dependent manner (8). In addition, i.v. infusion of PGE1 into humans has been shown to inhibit formyl-methionyl-leucyl-phenylalanine- (FMLP) induced lysosomal enzyme release from PMN (9). This study was undertaken to examine the effects of in vivo systemic treatment of rats with 15-M-PGE1 on FMLP-induced neutrophil lysosomal enzyme release and O2- secretion. As we will show, the modulation of FMLP-induced neutrophil function is correlated with a decrease in binding affinity for formyl-methionyl-leucyl-(3H)phenylalanine ((3H)-FMLP) to its specific receptor on the neutrophil plasma membrane. The data suggest a novel mechanism for the anti-inflammatory effects of prostaglandins of the E series.

Alprostadil↗
PubMed1983

Characterization of the rat neutrophil formyl peptide chemotaxis receptor.

Numerous synthetic N-formylated peptides, believed to be the analogs of the naturally occurring initiating signal peptides produced by bacteria, are potent chemotactic agents for phagocytic cells in several species. The authors have characterized the receptor with moderately high affinity for the chemotactic peptide f-Met-Leu-[3H]Phe on the rat peritoneal neutrophils. When neutrophils are incubated with f-Met-Leu-[3H]Phe at 24 C, the binding is saturable and reversible. The receptor on the inflammatory rat neutrophils has an equilibrium dissociation constant (KD) of 3.4 x 10(-8) M at 24 C, and there are approximately 65,000 sites per cell. In addition, the potency of several of these chemotactic peptides in inducing lysosomal enzyme secretion and superoxide production correlated well with their ability to compete with f-Met-Leu-[3H]Phe for receptor binding. Structure activity studies further demonstrate that the fine specificity of the formyl peptide receptor has been conserved across species lines.

Acetylglucosaminidase↗
PubMed1982

Papillary adenoma of the lung with lamellar and electron dense granules. An ultrastructural study.

An unusual papillary adenoma in the periphery of the lung was resected in a 25-year-old woman. Examination of the tumor showed a noninfiltrating cellular neoplasms consisting of cuboidal to columnar epithelial cells with eosinophilic granular cytoplasm and without nuclear atypia. Ultrastructurally the tumor cells had microvilli, infrequent cell junctions, and cytoplasmic dense granules and whorled lamellar membrane membrane inclusions. These findings suggest that this benign pulmonary neoplasm has morphologic characteristics consistent with a Clara Cell and alveolar type II pneumocyte differentiation. Although tumors of similar types can be experimentally induced in mice, and the light microscopic features of similar human neoplasms have been described, this is the first report of the ultrastructural characteristics of a benign human lung tumor with morphologic features resembling Clara cell and alveolar type II pneumocytes.

Adult↗
PubMed1982

Production of cyclooxygenase products and superoxide anion by macrophages in response to chemotactic factors.

Mononuclear phagocytes are known to play a key role in various phlogistic reactions by synthesizing and releasing products that may potentiate or inhibit inflammatory processes. The expression of these products appears to be dependent on the source of the macrophage population as well as the stimulus employed. We have studied superoxide anion (O-2) production as well as the generation of PGE2, PGF2 alpha, and TXB2 from resident, oil-elicited and thioglycollate-induced peritoneal macrophages in mice in the presence and absence of chemotactic peptides. Production of O-2, occurred only in elicited macrophages stimulated with high concentrations of FMLP or C5a; resident cells stimulated with either of the chemotactic peptides were completely unresponsive. Although resident peritoneal macrophages incubated with chemotactic peptides did not generate O-2, these cells did secrete significant levels of PGE2, PGF2 alpha, and TXB2 in response to C5a. FMLP had no stimulatory effect. Elicited macrophages generated increased levels of PGE2 and PGF2 alpha when incubated with C5a. However, production of TXB2 was not stimulated. FMLP was inactive in stimulating PGE2, PGF2 alpha, and TXB2 in all types of macrophages studied. These studies indicate a heterogeneity in the production of inflammatory mediators from various macrophage populations in response to chemotactic factors.

Animals↗
PubMed1982

Spasmogenic activity of chemotactic N-formylated oligopeptides: identity of structure--function relationships for chemotactic and spasmogenic activities.

The chemotactic N-formylated oligopeptides are potent spasmogenic agents for guinea pig ileum. Structure-activity studies with various N-formylated peptides suggest the presence of a specific receptor that resembles in specificity the formyl peptide receptor on leukocytes. A competitive antagonist of the formyl peptide receptor on leukocytes also inhibits formyl peptide-induced ileum contraction, whereas the antihistamine diphenhydramine is without effect. The contractile response caused by the synthetic N-formylated peptides differs from those induced by acetylcholine, histamine, and substance P. In particular, a latent period after treatment with the N-formyl peptides is seen before the onset of the response, and a sustained contractile response is not maintained. In addition, tachyphylaxis does occur, but complete recovery of activity is seen after a 20- to 30-min rest period. These observations suggest broad biological roles of prokaryotic signal peptides from bacteria as acute inflammatory mediators.

Animals↗
PubMed1982

Inhibition of vascular permeability changes in rats by captopril.

Systemic treatment of rats with captopril (50 mg/kg body wt per os), a specific competitive inhibitor of angiotensin l-converting enzyme, significantly inhibits vascular permeability changes induced by the intradermal injection of the vasoactive mediators histamine, bradykinin, serotonin, and compound 48/80. This effect of captopril is both dose- and time-dependent with approximately 60% inhibition of edema formation observed 7 h after captopril treatment (100 mg/kg body wt per os). The inhibitory effect of captopril on edema formation is temporally unrelated to the inhibition of serum angiotensin l-converting enzyme activity or serum prostaglandin E2 levels and is not inhibited by systemic treatment of rats with indomethacin. The data suggest that captopril may have potent antiinflammatory activity through as yet undefined mechanisms.

Animals↗