Immunopharmacological activities of a synthetic counterpart of a biosynthetic lipid A precursor molecule and of its analogs

Abstract

Synthetic lipid A analogs (compounds 404 through 406) were examined for their immunopharmacological activities. These compounds had two amide-bound and two ester-bound (R)-3-hydroxytetradecanoyl groups at the C-2 and C-2' and the C-3 and C-3' positions, respectively, of 0(1-6)glucosamine disaccharide. In all of the in vitro assays, these synthetic compounds exhibited high activities comparable to those of a reference lipid A prepared from Escherichia coli 08:K27 Re-mutant strain F515. The compounds activated the clotting enzyme cascade of the horseshoe crab, activated the human complement via the classical pathway, caused polyclonal B-cell activation, stimulated the phagocytosis of sheep erythrocytes by murine peritoneal macrophages, and

Deacylated lipopolysaccharide inhibits neutrophil adherence to endothelium induced by lipopolysaccharide in vitro.

“…Compared with LPS, deacylated LPS is 100-fold less active in the dermal Shwartzman reaction, although it still retains significant activity as a B cell mitogen (reference 10 and Figure 2). Similar behavior in these tests had been reported previously (25,26) for lipid A analogs that lack acyloxyacyl groups . In vitro, LPS induces an endothelial cell surface activity that promotes neutrophil adherence (1,2).…”

Possible Existence of a Novel Amphipathic Immunostimulator in the Phenol‐Water Extracts of Mycobacteriaceae

“…Examination of bioactivities in vivo and in vitro assay systems. Most of the assay methods were described in previous papers (15,33), and a brief description is given below.…”

Immunobiological activities of a chemically synthesized lipid A of Porphyromonas gingivalis

“…Three domestic Japanese white rabbits (male; 2^2.5 kg) per group were injected intravenously with the indicated doses of the test specimens in 10 ml of pyrogen-free PBS per kg as described previously [20]. The rectal temperature of each rabbit was measured and recorded continuously with an automatic device (EP670, 12; Iio Electric Co., Tokyo, Japan).…”