Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan.
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.
Ganz
Tomas
T
Department of Medicine, David Geffen School of Medicine, Los Angeles, CA 90095-1690, USA. tganz@mednet.ucla.edu
Gabayan
Victoria
V
Liao
Hsiang-I
HI
Liu
Lide
L
Oren
Ami
A
Graf
Thomas
T
Cole
Alexander M
AM
D000818:Animals; D001424:Bacterial Infections / Q000201:enzymology*; D004198:Disease Susceptibility / Q000201:enzymology; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D007249:Inflammation / Q000201:enzymology*; D008164:Luminescent Proteins / Q000235:genetics; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016982:Micrococcus luteus / Q000472:pathogenicity*; D009113:Muramidase / Q000032:analysis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009504:Neutrophils / Q000201:enzymology; D010457:Peptidoglycan; D011993:Recombinant Fusion Proteins
D008164:Luminescent Proteins; D010457:Peptidoglycan; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D009113:Muramidase; C472450:lysozyme M, mouse; C472773:lysozyme P, mouse