Chemotactic activity of aldehydes. Structural requirements. Role in inflammatory process.
The lipid peroxidation product 4-hydroxy-2,3-transnonenal (HNE) and its homologous compounds were found to induce a high significant stimulation of rat neutrophil oriented migration and morphological polarization at concentrations within a pico-micromolar range. These effects are weak with respect to the potent chemoattractant formyl-peptides. The structural requirements for the chemotactic activity of aldehydes were studied and the trans C-C double bond was found to be the essential requirement. The problem of the mechanism by which alpha, beta-unsaturated aldehydes interact with neutrophils is unsolved. With regard to this point, some hypotheses are discussed. The possibility that chemotactic unsaturated aldehydes are present in vivo in the inflammatory site at a concentration at which they are chemotactic in vitro was studied. Rat pleural exudates collected 1,2,3,4 hours after a pleurisy induction were analyzed and HNE was detected both in the supernatant of exudate and in cells. Its concentration in the liquid part of the exudate increased with time, in parallel with an increase in the number of cells in the exudate. It is reasonable that this aldehyde might be formed as a consequence of lipid peroxidation reactions concomitant to the phlogistic process. The hypothesis is proposed that HNE could participate in the neutrophil recruitment in the inflammatory area.
Curzio
M
M
Department of Medicine and Experimental Oncology, University of Turin.
Di Mauro
C
C
Esterbauer
H
H
Dianzani
M U
MU
D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D010998:Pleurisy / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D000447:Aldehydes; D008054:Lipid Peroxides