Modulation of human neutrophil function in vitro by gastrin

1997 ◽  
Vol 153 (3) ◽  
pp. 475-483 ◽  
Author(s):  
M De la Fuente ◽  
M Carrasco ◽  
A Hernanz

Abstract We have studied the effects in vitro of gastrin-17 and gastrin-34, at concentrations from 10−14 m to 10−6 m, on several of the functions of peripheral blood human neutrophils, i.e. adherence to substrate, mobility (spontaneous and directed by a chemical gradient or chemotaxis), ingestion of inert particles (latex beads) and cells (Candida albicans) and superoxide anion production. Both gastrins inhibited several steps of the phagocytic process of human neutrophils, such as mobility and ingestion. By contrast, these peptides increased adherence and had no effect on superoxide anion production. In general, these effects were significant at peptide concentrations between 10−12 m and 10−8 m with a maximal effect at 10−10 m. In addition, gastrin peptides induced a significant increase in intracellular cAMP levels at 30, 60 and 120 s. Moreover, the inhibitory effect of gastrin-17 on the ingestion capacity of neutrophils (latex bead phagocytosis) was similar to that obtained with EGTA, a well-known extracellular calcium chelating compound. Gastrin-17 was found to inhibit completely the stimulation of latex bead phagocytosis in neutrophils caused by the calcium ionophore A23187. These results suggest that gastrin is a negative modulator of the phagocytic process of human neutrophils, and that this effect might involve an increase in intracellular cAMP levels and a decrease in calcium entry into the cells. Journal of Endocrinology (1997) 153, 475–483

1999 ◽  
Vol 44 (3) ◽  
pp. 337-341 ◽  
Author(s):  
Ken Sato ◽  
Noriyuki Sato ◽  
Hiroyuki Shimizu ◽  
Takahumi Tsutiya ◽  
Hiroki Takahashi ◽  
...  

1992 ◽  
Vol 262 (1) ◽  
pp. L63-L68 ◽  
Author(s):  
R. S. Oosting ◽  
J. F. Van Iwaarden ◽  
L. Van Bree ◽  
J. Verhoef ◽  
L. M. Van Golde ◽  
...  

This study focused on the question of whether exposure of surfactant protein A (SP-A) to ozone affected properties of this protein that may be involved in regulating alveolar type II cell and alveolar macrophage functions. In vitro exposure of human or canine SP-A to ozone reduced the ability of this protein to inhibit phorbol-ester induced secretion of [3H]phosphatidylcholine by alveolar type II cells in culture. Ozone-exposed human SP-A showed a decreased ability to enhance phagocytosis of herpes simplex virus and to stimulate superoxide anion production by alveolar macrophages. Experiments with elastase showed that ozone-exposed canine SP-A was more susceptible to proteolysis. A conformational change of the protein could underlie this phenomenon. Surfactant isolated from ozone-exposed rats (0.4 ppm ozone for 12 h) was also less able to stimulate superoxide anion production by alveolar macrophages than surfactant from control rats, which suggested that SP-A in vivo was also susceptible to ozone. The results of this study suggest that SP-A-alveolar cell interactions can be inhibited by ozone exposure, which may contribute to the toxicity of ozone in the lungs.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amina Chniguir ◽  
Coralie Pintard ◽  
Dan Liu ◽  
Pham My-Chan Dang ◽  
Jamel El-Benna ◽  
...  

AbstractEugenol is a polyphenol extracted from Syzygium aromaticum essential oil. It is known to have anti-inflammatory and chemoprotective properties as well as a potent anti-oxidant activity due the presence of its phenolic group. In this study, we examined the effects of eugenol on neutrophil superoxide production, a key process involved in innate immunity and inflammation. Superoxide anion generationin human neutrophils was measured by cytochrome c reduction assay. Western blotting was used to analyze the phosphorylation of, p47phox, MAPKinases (p38 and ERK1/2), MEK1/2 and Raf, key proteins involved in the activation of NADPH oxidase. Pretreatment of neutrophils by increasing concentrations (2.5 µg/mL–20 µg/mL) of eugenol for 30 min, inhibited significantly (p < 0.001) superoxide anion generation induced by the chemotactic peptide formyl-Met-Leu-Phe (fMLF) with an IC50 of 5 µg/mL. Phorbolmyristate acetate (PMA)-stimulated O2− production was affected only at the highest eugenol concentration (20 µg/mL). Results showed that eugenol decreased the phosphorylation of p47phox onSer-345 and Ser-328, the translocation of p47phox to the membranesand the phosphorylation of Raf, MEK1/2 and ERK1/2 proteins. Taken together, our results suggest that eugenol inhibits the generation of superoxide anion by neutrophils via the inhibition of Raf/MEK/ERK1/2/p47phox-phosphorylation pathway.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Milene Valéria Lopes ◽  
Vânia Cristina Desoti ◽  
Angelo de Oliveira Caleare ◽  
Tânia Ueda-Nakamura ◽  
Sueli Oliveira Silva ◽  
...  

Here we demonstrate the activity of geranylgeraniol, the major bioactive constituent from seeds ofBixa orellana, againstLeishmania amazonensis. Geranylgeraniol was identified through1H and13C nuclear magnetic resonance imaging and DEPT. The compound inhibited the promastigote and intracellular amastigote forms, with IC50of11±1.0and17.5±0.7 μg/mL, respectively. This compound was also more toxic to parasites than to macrophages and did not cause lysis in human blood cells. Morphological and ultrastructural changes induced by geranylgeraniol were observed in the protozoan by electronic microscopy and included mainly mitochondria alterations and an abnormal chromatin condensation in the nucleus. These alterations were confirmed by Rh 123 and TUNEL assays. Additionally, geranylgeraniol induces an increase in superoxide anion production. Collectively, ourin vitrostudies indicate geranylgeraniol as a selective antileishmanial that appears to be mediated by apoptosis-like cell death.


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