The Lipid Peroxidation Product 4-Hydroxynonenal is Formed by - and is able to Attract - Rat Neutrophilsin vivo

Abstract

4-Hydroxynonenal (HNE), a major aldehydic product of lipid peroxidation, is a chemoattractant for neutrophilic polymorphonuclear granulocytes in vitro. The question was studied, whether HNE is formed during the ingress of neutrophils in the Sephadex model of inflammation. The polydextrane Sephadex G-200, which causes an acute aseptic traumatic inflammation, was injected subcutaneously into rats. The implants were excised 6-36 hours later, and the neutrophils separated from the exsudate by centrifugation. After extraction with dichloromethane HNE was identified in the exsudate by non-derivative reversed phase HPLC in combination with on-line uv-spectroscopy. The concentration of HNE in the inflammatory focus did not correlate with the number of neutrophils present. While the peak of HNE coincided with the time point of the highest turnover rate of neutrophils (0.13 microM at 6 hrs after implantation), the highest number of neutrophils (about 100 million cells) occurred not earlier than 18 hrs later (24 hrs after onset of inflammation). When neutrophils were isolated from the inflammatory focus and stimulated with Zymosan, they were able to produce HNE in vitro depending on the time of isolation. The highest production of HNE (0.17 microM) by phagocyting neutrophils was observed at the shortest inflammation time studied (3 hrs). In order to compare these results with the oxidative burst of neutrophils the formation of superoxide was also measured by the cytochrome c reduction assay in vitro. The maximum of the production rate of superoxide anion was observed at the same inflammation time (6 hrs), when the HNE maximum occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte‐macrophages

“…It was suggested that either only a certain subpopulation of neutrophils react to HNE, or that the neutrophils, which were derived from pleural exudate, had been desensitized by previous exposure to HNE in vivo. Indeed, HNE was demonstrated to act as a chemoattractant for rat neutrophils in vivo and to desensitize the cells to subsequent HNE exposure [27,28]. In our experiments the number of monocytes responding to HNE was only slightly lower than that for fMLP (78%).…”

Tissue Occurrence of Carbonyl Products of Lipid Peroxidation and Their Role in Inflammatory Disease

“…The cell migration can be evaluated under the light microscope by the leading front technique. The first demonstration of HNE chemotactic power was obtained "in vitro", but afterwards it was confirmed by Schaur et al [20] who carried on "in vivo" experimental researches. They induced an aseptic inflammation in the subcutaneous tissue of a rat leg by injecting in it some polydextrane Sephadex G-200; in control rats they inoculated Sephadex alone, while in the experimental group of rats they inoculated Sephadex together with a solution of preformed HNE.…”

“…In fact low levels of the lipid peroxidation end products have been shown in tissues even in normal conditions [20]. The rate of the lipid peroxidation can be stimulated by the ROS and the free radicals which can arise also from the normal metabolism of cells.…”

Cigarette smoke and α,β‐unsaturated aldehydes elicit VEGF release through the p38 MAPK pathway in human airway smooth muscle cells and lung fibroblasts

“…We observed that 4-HNE was capable of activating, at sub-toxic concentrations, VEGF release from ASMC cultures. Interestingly, 4-HNE also stimulated the secretion of IL-8 in macrophages (Facchinetti et al, 2007), lung fibroblasts and epithelial cells (Moretto et al, 2009) as well as eliciting neutrophil recruitment (Schaur et al, 1994). Thus, VEGF might be triggered in chronic cigarette smokers or COPD patients not only by smoke-inhaled acrolein and crotonaldehyde, but also by endogenously formed unsaturated aldehydes such as 4-HNE.…”