title: Elevated neutrophil elastase and acrolein-protein adducts are associated with W256 regression.
abstract: The involvement of granulocytes in immune response against cancer is not well understood. Depending on the cytokine milieu in which they act and on their oxidative burst, granulocytes may play either an inhibitory or stimulatory role in tumour growth. Unsaturated fatty acids, essential components of cellular membranes and storage lipids, are susceptible to granulocyte-derived reactive oxygen species (ROS). ROS can induce lipid peroxidation (LPO) resulting in the destruction of biomembranes. Thus, murine W256 tumour progressing and tumour regressing animal models were used to study the involvement of plasma inflammatory mediators and oxidative burst of circulating granulocytes in malignant destruction and detrimental tumour growth. The involvement of LPO-derived aldehydes (i.e. acrolein, 4-hydroxy-2-nonenal and malondialdehyde) and myeloperoxidase (MPO) appearance in the granulocyte anti-cancer response were further evaluated. The results obtained revealed a significant increase in neutrophil elastase in animals with regressing tumour. Furthermore, the presence of MPO in tumour microenvironment was accompanied by the formation of acrolein only 5 h after tumour transplantation and its presence increased during tumour regression. Later, at an early stage of tumour regression, the presence of other LPO-derived aldehydes were also observed. The results obtained suggest that elevated neutrophil elastase and initiation of LPO may play an important role in the tumour development leading to tumour regression.
authors.affiliation: Department of Molecular Medicine, Rudjer Boskovic Institute Department of Pathology, Medical Faculty, University of Zagreb, Clinical Hospital Centre Zagreb, Zagreb, Croatia. morana.jaganjac@irb.hr
authors.forename: M
authors.initials: M
authors.lastname: Jaganjac
authors.forename: M
authors.initials: M
authors.lastname: Poljak-Blazi
authors.forename: R J
authors.initials: RJ
authors.lastname: Schaur
authors.forename: K
authors.initials: K
authors.lastname: Zarkovic
authors.forename: S
authors.initials: S
authors.lastname: Borovic
authors.forename: A
authors.initials: A
authors.lastname: Cipak
authors.forename: M
authors.initials: M
authors.lastname: Cindric
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: G
authors.initials: G
authors.lastname: Waeg
authors.forename: N
authors.initials: N
authors.lastname: Zarkovic
mesh_terms: D000171:Acrolein / Q000276:immunology / Q000378:metabolism*; D000447:Aldehydes / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D018450:Disease Progression; D005231:Fatty Acids, Unsaturated / Q000276:immunology / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology* / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019272:Leukocyte Elastase / Q000276:immunology / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000276:immunology / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology / Q000502:physiology; D059016:Tumor Microenvironment / Q000276:immunology* / Q000502:physiology
chemical_list: D000447:Aldehydes; D005231:Fatty Acids, Unsaturated; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000171:Acrolein; D019272:Leukocyte Elastase