Role of polymorphonuclear leukocytes in connective tissue breakdown during the reverse passive Arthus reaction.
The reverse passive Arthus (RPA) reaction performed in the skin of rats was modified to allow for the determination of polymorphonuclear leukocyte (PMN) infiltration and hemorrhage, as well as changes in vascular permeability. After initiation of the RPA reaction, PMN infiltration, monitored by measurement of tissue myeloperoxidase (MPO, EC 1.11.1.7) content, increased dramatically with time. Depending on the experimental conditions used, PMN accumulation reached a maximum 2-10 hr after increased vascular permeability (125I-labeled albumin content) had peaked. Hemorrhage (59Fe-labeled erythrocyte accumulation) began to occur only after significant levels of PMN were reached and continued to increase proportionately to the level of PMN infiltration attained. Indomethacin administered 30 min prior to initiating the RPA reaction had no effect on vascular permeability increase but suppressed both PMN accumulation and hemorrhage development about 50%. When indomethacin was given 2 hr after the RPA reaction was begun, no effect on any of the RPA variables was noted. Dexamethasone suppressed the increase in vascular permeability (53%), PMN accumulation (78%), and hemorrhage (90%) when given 30 min prior to initiation of the reaction. Dexamethasone given 2 hr after initiating the RPA suppressed the entire reaction, but to a lesser extent. Catalase, as well as trasylol, alpha-1-antiproteinase and soybean trypsin inhibitor, inhibited PMN accumulation as well as hemorrhage when given intravenously at plus 2 hr. These results indicate that the damage to blood vessels during a severe RPA reaction is a direct consequence of PMN activity.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001183:Arthus Reaction / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D003238:Connective Tissue / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006470:Hemorrhage / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000032:analysis; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D011480:Protease Inhibitors; D009195:Peroxidase; D007213:Indomethacin