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Prolonged lung edema formation during the generalized Shwartzman reaction in rabbits--can it be a model for septic
1First Department of Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abstract:
Pulmonary edema formation and the role of polymorphonuclear leukocytes (PMN) was evaluated during the generalized Shwartzman reaction (GSR) model in rabbits. Chemiluminescence (CL) and superoxide (O2-) production activity stimulated by FMLP were measured in circulating PMN after a single intravenous injection of endotoxin (E. coli 026:B6, 40 micrograms/kg) (E1). CL peaked at 36 hr after E1 injection and then decreased gradually to a normal range within 7 days. O2- production changed in a similar fashion. On the other hand, the PMN count peaked at 72 hr and remained at a high value until day 7. To induce GSR, a second venous injection of endotoxin (40 micrograms/kg) (E2) was administered 36 hr after the first one (E1). Four times as many PMN were observed in the lung capillaries 4 hr after the second endotoxin injection than after the first endotoxin injection (4 hr). The degree of lung edema formed increased after E2, but did not increase after E1. An alveolar hyaline-like exudate was observed 24 hr after E2. A continuous intravenous injection of superoxide dismutase (SOD) plus catalase or PMN depletion, prevented the development of post-E2 lung edema. If E2 was given 7 days after E1, no lung edema formed at all. These data indicate that oxygen free radicals from activated PMN by endotoxin play an important role in prolonged lung edema formation in the GSR model.
Insights
Polymorphonuclear leukocytes (PMN) activation by endotoxin causes lung edema during the generalized Shwartzman reaction (GSR). Antioxidant enzymes and PMN depletion prevent this edema, highlighting the role of reactive oxygen species.
Area of Science:
- Immunology
- Pathophysiology
- Pulmonary Medicine
Background:
- The generalized Shwartzman reaction (GSR) is a model for studying endotoxin-induced responses.
- Polymorphonuclear leukocytes (PMN) are implicated in inflammatory processes, including lung injury.
Purpose of the Study:
- To investigate the role of PMN and reactive oxygen species in pulmonary edema formation during the GSR in rabbits.
- To evaluate the effect of PMN activation and endotoxin challenge on lung edema.
Main Methods:
- Rabbits received an initial endotoxin injection (E1), followed by a second injection (E2) to induce GSR.
- Circulating PMN activity (chemiluminescence, superoxide production) and counts were measured.
- Lung PMN infiltration and edema formation were assessed.
- Interventions included superoxide dismutase (SOD) plus catalase and PMN depletion.
Main Results:
- Endotoxin challenge increased PMN activity and counts, with PMN counts peaking at 72 hours.
- The second endotoxin injection (E2) significantly increased PMN infiltration in lung capillaries and induced pulmonary edema.
- Antioxidant treatment (SOD + catalase) or PMN depletion prevented edema formation.
- Edema did not develop if the second endotoxin injection was delayed by 7 days.
Conclusions:
- Activated PMN, through the production of oxygen free radicals, play a critical role in endotoxin-induced pulmonary edema during the GSR.
- The timing of endotoxin challenge is crucial for the development of lung edema in this model.