β2-Adrenoceptors inhibit neutrophil extracellular traps in human polymorphonuclear leukocytes

Abstract

This study tests the hypothesis that in isolated human polymorphonuclear leukocytes (PMN) adrenergic ligands can affect neutrophil extracellular trap (NET) formation. We have previously shown that, in PMN, adrenaline (A), through the activation of adrenergic receptors (AR), reduces stimulus-dependent cell activation; we have, therefore, planned to investigate if AR are involved in NET production. PMN were obtained from venous blood of healthy subject. The ability of adrenergic ligands to affect reactive oxygen species (ROS) production, NET production, and cell migration was investigated in cells cultured under resting conditions or after activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP), LPS, or IL-8. Stimuli-induced NET production measured as ROS, microscopic evaluation, and elastase production was reverted by A and this effect was blocked by the selective β -AR antagonist ICI-118,551. The stimulus-induced ROS generation and migration was prevented by A and by isoprenaline (ISO), and these effects were counteracted only by ICI-118,551 and not by the other two selective ligands for the β and β -AR. Finally, the presence of the β-ARs on PMN was confirmed, by means of microscopy and flow cytometry. The data of the present study suggest that adrenergic compounds, through the interaction of mainly β -AR, are able to affect neutrophil functions. These data are suggestive of a possible therapeutic role of β -AR ligands (in addition to their classical use), promoting the possible therapeutic relevance of adrenergic system in the modulation of innate immunity proposing their possible use as anti-inflammatory drugs.

Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: A case series

“…All patients received the same treatment doses: nebulized dornase alfa (2.5 mg) co-administered twice daily with the short-acting β 2 -agonist albuterol (2.5 mg, hereafter abbreviated as nDA+A) to improve delivery to the alveoli. Of note, β 2 -adrenoreceptor agonism may also inhibit NET formation by direct action on neutrophils (14). The treatment was administered with an Aerogen® Solo in-line nebulizer to avoid open aerosol generation, which would place staff at risk of exposure to SARS-CoV-2.…”

The role of neutrophils in neuro-immune modulation

“…Recent studies showed that neutrophils express both αARs and βARs including α 1A , α 2C , α 1D , β 1 , β 2 , and β 3 ARs but not α 2B ARs mRNA [52,[58][59][60][61][62][63]. The expression of αARs in neutrophils has been confirmed in multiple studies related to diverse physiological conditions [52,61].…”

“…βARs are predominantly anti-inflammatory. in vitro studies showed that βARs modulate neutrophil oxidative burst, chemotaxis, NET formation, and the expression of adhesion molecules, leukotriene B 4 (LTB 4 ), and chemokines/cytokines [62][63][64][65]. The intracellular βAR signaling, especially those associated with cAMP and PKA activation, modulate most to the neutrophil functions [66,67].…”

A Novel Standardized Cannabis sativa L. Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functions

“…PMN migration was investigated by the Boyden chamber assay modified as previously described [46]. Briefly, after instrument assembly, PMN at 1 × 10 6 cells/mL in RPMI 1640 medium were placed in the upper chamber alone or together with the test substance, while the lower chamber contained medium alone (spontaneous migration) or added with 10 ng/mL interleukin (IL)-8 (Sigma–Aldrich, code: I1645) or 0.1 μM N-formyl-Met-Leu-Phe (fMLP, Sigma–Aldrich, code: F3506) (stimulated migration).…”