Effect of Hydrogen Sulfide on Essential Functions of Polymorphonuclear Leukocytes

Abstract

Impaired polymorphonuclear leukocyte (PMNL) functions contribute to increased infections and cardiovascular diseases in chronic kidney disease (CKD). Uremic toxins reduce hydrogen sulfide (H2S) levels and the anti-oxidant and anti-inflammatory effects of H2S. Its biosynthesis occurs as a side process of transsulfuration and in the disposal of adenosylhomocysteine, a transmethylation inhibitor and proposed uremic toxin. PMNL chemotaxis was measured by the under-agarose method, phagocytosis, and oxidative burst by flow cytometry in whole blood and apoptosis by determining DNA content by flow cytometry and morphological features by fluorescence microscopy. Sodium hydrogen sulfide (NaHS), diallyl trisulphide (DATS) and diallyl disulphide (DADS), cysteine, and GYY4137 were used as H2S-producing substances. Increased H2S concentrations did not affect chemotaxis and phagocytosis. NaHS primed PMNL oxidative burst activated by phorbol 12-myristate 13-acetate (PMA) or E. coli. Both DATS and cysteine significantly decreased E. coli-activated oxidative burst but had no effect on PMA stimulation. While NaHS, DADS, and cysteine attenuated PMNL apoptosis, GYY4137 decreased their viability. Experiments with signal transduction inhibitors suggest that the intrinsic apoptosis pathway is mainly involved in GYY4137-induced PMNL apoptosis and that GYY4137 and cysteine target signaling downstream of phosphoinositide 3-kinase.

Plants and Mushrooms as Possible New Sources of H2S Releasing Sulfur Compounds

“…The molecular mechanisms by which H 2 S reduces leukocyte migration and adhesion in various experiments are different: activation of different classes of potassium channels [49], induction of heme oxygenase-1 [50], and downregulation of CD11b expression [51]. However, in the presence of a strong pro-inflammatory stimulus, H 2 S stimulates neutrophil tissue adhesion and infiltration [52] through the upregulation of adhesion receptors, such as intercellular adhesion molecule 1 (ICAM-1) and P-selectin [53]. It is not contradictory with data reported earlier: under a septic condition, an increase in leukocyte infiltration is desirable since the organism is compromised.…”

Hydrogen Sulfide and Oxygen Homeostasis in Atherosclerosis: A Systematic Review from Molecular Biology to Therapeutic Perspectives

“…H 2 S can interact with several signaling pathways involved in the pathogenesis of atherosclerosis, including the PI3K/Akt, MAPK/ERK, and NF-κB pathways [31]. The PI3K/Akt pathway plays a critical role in cell survival, proliferation, and apoptosis.…”

“…Moreover, H 2 S has been found to regulate endothelial function by stimulating the release of nitric oxide (NO), a potent vasodilator that plays a key role in maintaining vascular homeostasis. In addition, H 2 S modulates the inflammatory response by inhibiting the activation of nuclear factor kappa B (NF-κB) and promoting the production of anti-inflammatory cytokines [31]. H 2 S can also protect against oxidative stress by eliminating reactive oxygen species (ROS) and increasing the expression of antioxidant enzymes [32], such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) [33].…”

Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis—A Comprehensive One-Year Review

“…This shift in perception is due to the recognition of H 2 S as a significant player in diverse physiological and pathological processes [ 4 ]. This small molecule, considered as the third gasotransmitter alongside nitric oxide (NO) and carbon monoxide (CO), exerts a plethora of effects in mammalian physiology, such as vasodilation [ 5 ], vascular tone [ 6 ], modulating the inflammatory response [ 7 , 8 ], neurotransmission [ 9 ], antioxidant properties [ 10 ], apoptosis [ 11 ] cellular survival [ 12 ], regulating cellular metabolism [ 13 ], or acting as a cytoprotectant [ 14 ]. As a multifaceted molecule [ 15 , 16 ] with profound biological implications, H 2 S has increasingly been at the center of scientific scrutiny.…”