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Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan
Tomas Ganz1, Victoria Gabayan, Hsiang-I Liao
1Department of Medicine, David Geffen School of Medicine, Los Angeles, CA 90095-1690, USA. tganz@mednet.ucla.edu
Abstract:
More than 70 years ago, Alexander Fleming discovered lysozyme and proposed that nonpathogenic bacteria fail to cause disease because they are very susceptible to destruction by lysozyme, an enzyme that is one of the principal proteins of phagocytes. Although much has been learned about the effects of lysozyme in vitro, its biological role in vivo has not been determined. We examined transgenic mice deficient in lysozyme M after challenge by the normally nonpathogenic and highly lysozyme-sensitive bacterium Micrococcus luteus. Despite partial compensation by newly expressed lysozyme P in macrophages, lysozyme M-deficient mice developed much more severe lesions than wild-type mice. The tissue injury was due to the failure of lysozyme M-deficient mice to inactivate peptidoglycan, resulting in an intense and prolonged inflammatory response. Our data indicate that tissue injury is normally limited by prompt degradation of bacterial macromolecules that trigger innate immunity and inflammation.
Insights
Lysozyme M deficiency in mice leads to severe tissue injury and prolonged inflammation when exposed to Micrococcus luteus. This highlights lysozyme M's crucial role in controlling innate immunity and preventing inflammatory damage.
Area of Science:
- Immunology
- Microbiology
- Enzymology
Background:
- Lysozyme, discovered by Alexander Fleming, is a key enzyme in innate immunity.
- Its in vitro functions are known, but its in vivo biological role remains unclear.
- Phagocytes utilize lysozyme to degrade bacteria.
Purpose of the Study:
- To investigate the in vivo role of lysozyme M in host defense.
- To determine the consequences of lysozyme M deficiency on inflammatory responses.
- To understand the mechanism of tissue injury caused by lysozyme M deficiency.
Main Methods:
- Generation of transgenic mice deficient in lysozyme M.
- Challenge of these mice with the bacterium Micrococcus luteus.
- Assessment of lesion severity, inflammatory response, and peptidoglycan inactivation.
Main Results:
- Lysozyme M-deficient mice exhibited significantly more severe lesions compared to wild-type mice.
- Despite lysozyme P compensation in macrophages, bacterial inactivation was impaired.
- Failure to degrade peptidoglycan resulted in intense and prolonged inflammation.
Conclusions:
- Lysozyme M plays a critical role in vivo in controlling inflammation and preventing tissue injury.
- Prompt degradation of bacterial macromolecules by lysozyme M limits inflammatory responses.
- Lysozyme M is essential for effective host defense against susceptible bacteria.