A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation

Abstract

Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation.

Acrolein and other toxicant exposures in relation to cardiovascular disease among marijuana and tobacco smokers in a longitudinal cohort of HIV-positive and negative adults

“…These findings are consistent with a previous cohort study reporting higher urinary 3HPMA concentrations in smokers compared with nonsmokers, and associations between increased 3HPMA and CVD risk measures including platelet-leukocyte aggregates and Framingham Risk score [20]. Previous studies have shown acrolein exposures can induce cardiovascular injury in animal models [17,19], induce or exacerbate dyslipidemia, and modify lipoproteins [43,44], and may contribute to neutrophil-mediated inflammation [45]. HIV infection is associated with increased inflammation [46,47] and renal dysfunction [48], which may further increase acrolein levels and its impact on cardiovascular disease [16,39,42,49].…”

Obesity significantly alters the human sperm proteome, with potential implications for fertility

“…Due to its potent capacity for degrading PGP, reduced abundance of this protein could help to sustain local inflammation in the testes. Interestingly, both the production and activity of LTA4H is reduced by acrolein [39], a byproduct of lipid peroxidation, which could be produced by developing spermatozoa undergoing oxidative stress [40]. While inflammation associated with obesity is primarily propelled by adipose tissue, reduced levels of SUGT1 and LTA4H could help to maintain inflammation in the testes of obese men.…”

Panton-Valentine Leukocidin associated with S. aureus osteomyelitis activates platelets via neutrophil secretion products

“…PVL additionally increased the formation of acrolein-bound proteins in neutrophil-conditioned plasma. Acrolein is generated by human neutrophils via the myeloperoxidase/hydrogen peroxide/chloride system 21 and by other mechanisms, and has been associated with exacerbated inflammatory and immune responses 39 , 40 as well as with ischemic stroke 41 .…”