Modification of immunopharmacological activities of synthetic monosaccharide lipid A analogue, GLA60, by lysozyme.
Recent studies by our group suggested that lysozyme has a high affinity for bacterial lipopolysaccharide (LPS) of both the smooth and rough forms, and inhibits various immunomodulatory activities of LPS. GLA60 is a synthetic monosaccharide analogue of bacterial lipid A well known as having most of the activities of lipid A with very low toxicity. In this study, we characterized the interaction of lysozyme with GLA60 in comparison to that with Escherichia coli 0111 LPS (smooth form) by means of an immunopharmacological approach. Using dansylated lysozyme (DNS-LZM) as a probe, LZM was found to bind to GLA60. The mitogenic and polyclonal B-cell activating activities were significantly reduced by complex formation. However, there was no inhibitory effect on GLA60 induced production of IL-1 and TNF of macrophages. Interestingly, the activities of macrophages induced by the complex were found to be significantly higher than those induced by GLA60 itself. In contrast, the activities of 0111 LPS were significantly inhibited by LZM. Since the GLA60-LZM complex produced a turbid suspension but the 0111 LPS-LZM complex remained soluble, we consider that the activities of GLA60 alone were mediated by the common functional LPS receptor for dispersed form in both macrophages and B-lymphocytes, but activation of macrophages by the complex was mediated either by another LPS receptor not present in B-lymphocytes or through the phagocytic function of macrophages.
Tanida
N
N
Laboratory of Immunopharmacology of Microbial Products, Tokyo College of Pharmacy.
Ohno
N
N
Adachi
Y
Y
Matsuura
M
M
Nakano
M
M
Kiso
M
M
Hasegawa
A
A
Yadomae
T
T
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D003619:Dansyl Compounds / Q000737:chemistry; D007375:Interleukin-1 / Q000096:biosynthesis; D008050:Lipid A / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008934:Mitogens; D009113:Muramidase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D003619:Dansyl Compounds; D007375:Interleukin-1; D008050:Lipid A; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; C056260:GLA 60; D009113:Muramidase