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Differential alterations in host peripheral polymorphonuclear leukocyte chemiluminescence during the course of
Abstract:
Previous studies have shown that stimulation of the oxidative metabolism in polymorphonuclear leukocytes (PMN) by in vitro phagocytosis of various microorganisms results in photon emission, termed chemiluminescence (CL). Studies were conducted to determine whether bacterial and viral infections induce enhanced basal endogenous host peripheral PMN CL in the absence of in vitro phagocytic stimulation. Nonimmune rats and guinea pigs as well as immune rats were inoculated with various doses (10(5) to 10(7)) of live vaccine strain Francisella tularensis (per 100 g of body weight). In addition, nonimmune guinea pigs were inoculated with 40,000 plaque-forming units of Pichinde virus. Luminol-assisted endogenous PMN CL was measured at various time intervals after inoculation of microorganisms. Enhanced endogenous PMN CL was detected as early as the appearance of fever (12 h) in nonimmune animals infected with F. tularensis. Addition of sodium azide, N-ethylmaleimide, superoxide dismutase, or catalase to the CL reaction mixture containing PMN from infected animals significantly decreased the CL response. Immune rats challenged with F. tularensis exhibited resistance to infection and a decreased PMN CL compared with nonimmune rats 24 and 48 h after inoculation. However, the CL response from immune rats was significantly elevated, compared with control values. In contrast to the results obtained with the model bacterial infection, PMN isolated from guinea pigs inoculated with Pichinde virus failed to exhibit enhanced CL, compared with controls, despite significant viremia and fever. Results suggest that enhanced endogenous CL during bacterial infection occurs through mechanisms involving increased PMN oxidative metabolism and the subsequent generation of microbicidal forms of oxygen. Further, measurement of endogenous PMN CL may have diagnostic and prognostic value in infectious diseases.
Insights
Bacterial infections increase polymorphonuclear leukocyte (PMN) chemiluminescence (CL) in rats, indicating heightened oxidative metabolism. This endogenous PMN CL may serve as a diagnostic marker for infectious diseases.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Polymorphonuclear leukocytes (PMN) exhibit chemiluminescence (CL) upon stimulation of oxidative metabolism during phagocytosis.
- Previous research established a link between PMN oxidative metabolism and CL.
- The role of endogenous PMN CL in response to in vivo infections was not well understood.
Purpose of the Study:
- To investigate if bacterial and viral infections induce enhanced basal endogenous PMN CL in the absence of in vitro stimulation.
- To explore the potential diagnostic and prognostic value of endogenous PMN CL in infectious diseases.
Main Methods:
- Infection of nonimmune and immune rats with Francisella tularensis.
- Infection of nonimmune guinea pigs with Pichinde virus.
- Measurement of luminol-assisted endogenous PMN CL at various time points post-inoculation.
- Assessment of the involvement of reactive oxygen species by adding inhibitors (sodium azide, N-ethylmaleimide, superoxide dismutase, catalase).
Main Results:
- Enhanced endogenous PMN CL was detected in rats infected with F. tularensis as early as 12 hours post-infection, coinciding with fever.
- Inhibition studies confirmed the involvement of oxidative metabolism and reactive oxygen species in the enhanced CL.
- Immune rats showed reduced PMN CL compared to nonimmune rats, but still elevated compared to controls.
- PMN from guinea pigs infected with Pichinde virus did not exhibit enhanced CL despite viremia and fever.
Conclusions:
- Enhanced endogenous PMN CL during bacterial infection is mediated by increased PMN oxidative metabolism and the generation of microbicidal oxygen forms.
- Endogenous PMN CL measurement shows potential as a diagnostic and prognostic tool for bacterial infections.
- Viral infections, unlike bacterial infections, did not elicit a significant endogenous PMN CL response in this study.