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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)

In the search for objective methods to monitor the course of wound healing, the proteinase PMN elastase (n=56 pat.), the lipid peroxidation product malondialdehyde (MDA) (n=18 pat.), and polymorphonuclear neutrophil granulocytes (PMN) migratory behaviour were measured [1, 6, 7, 11]. This "stimulated PMN-locomotion" was quantified by a new PMN migration filter assay (n=10 pat.) [2]. We determined the clinical course during "per primam (pp)" wound healing (group 1), "pp" wound healing with secondary inflammatory disease (group 2), manifestation of a bacterial wound infection during healing-"per secundam (ps)" (group 3) and manifest wound infection ("ps") at the time of admission (group 4).In group 1 PMN elastase returned to normal values on the 10th postsurgical day. Median values in group 3 reflected a highly significant difference (p<0,01) on day 4 and 5 compared with group 1. In group 2 and 4 medians reflected consistent high values without reaching normal ranges throughout. MDA did not exceed the normal range in group 1, in group 3 low levels persisted, and in group 4 a recurring increase was noticed.The total migration index median (TMI) in Group I, which quantifies the percentage of stimulated PMN, reflected its highest value immediately post-surgically and dropped to the lowest on the 13th postsurgical day (decrease by 54%). The mean invasion depth (T/2), a parameter of PMN distribution, showed only slight variation with time. In a group 3-patient, T/2 reflected a maximal migratory stimulation on day 6, 4 days before clinical infection signs could be noticed; then it dropped to the lowest on day 10. This decrease probably reflects a PMN behavioural change from migration to phagocytosis [9].

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