title: Erythrocytes protect alpha-1-proteinase inhibitor from oxidative inactivation induced by chemicals, the myeloperoxidase-H2O2-halide system and stimulated polymorphonuclear leukocytes.
abstract: The oxidative inactivation of the alpha-1-proteinase inhibitor (alpha 1PI) is one of the mechanisms responsible for creating the elastase/antielastase imbalance during inflammation in the lower respiratory tract. Chronic supremacy of elastase may cause degradation of elastin fibers leading to the pulmonary emphysema. In this study we have investigated the effect of erythrocytes (RBC, concentrations 0.125 to 1.5%) on the oxidative inactivation of alpha 1PI by the phorbol myristate acetate-stimulated polymorphonuclear leukocytes (PMNL) and PMNL myeloperoxidase-H2O2-halide system. During exposure of alpha 1PI to both systems in the presence of RBC the significant protection (p less than 0.001) of alpha 1PI was found for all RBC concentrations, e.g. at RBC concentration of 1% the elastase inhibitory capacity (EIC) of alpha 1PI increased from 0 to 60 +/- 6 and 88 +/- 9% of the control value (untreated alpha 1PI), n = 5, respectively. The preincubation of RBC with chloramine-T (1 mM), inhibition of RBC catalase or depletion of RBC reduced glutathione alone did not diminish the capacity of RBC to protect alpha 1PI. However, these treatments together completely deprived RBC of their protective properties. Moreover, we have compared the decrease in the EIC of human blood and its plasma after incubation with H2O2 (0.1 mM to 0.1 M) or chloramine-T (1 microM to 1 mM). For the incubation with H2O2 no decrease in blood EIC was found whereas in plasma the loss of EIC was already visible at a H2O2 concentration of 0.1 mM. Also for the incubation with chloramine-T the EIC of blood was more resistant to oxidant damage than EIC of plasma. It is suggested that RBC contaminations present in the phagocyte inflammatory infiltration in the lower airways may protect alpha 1PI from oxidative inactivation and thus indirectly diminish proteolytic lung injury related to inflammation.
authors.affiliation: Department of Pneumology and Allergology, Medical Academy, Lódź, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Nowak
authors.forename: G
authors.initials: G
authors.lastname: Piasecka
mesh_terms: D002700:Chloramines / Q000494:pharmacology; D004912:Erythrocytes / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology*; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase / Q000378:metabolism / Q000502:physiology; D009195:Peroxidase / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D002700:Chloramines; D000515:alpha 1-Antitrypsin; D006861:Hydrogen Peroxide; D009195:Peroxidase; D010196:Pancreatic Elastase; C030816:chloramine; D013755:Tetradecanoylphorbol Acetate