calcimycin and Staphylococcal-Infections

The treatment of abscess homogenates with calcium ionophores stimulated the production of a bactericidal lipid with properties indistinguishable from those of a previously unidentified bactericidal lipid that had been detected in staphylococcal abscesses. The lipid was identified as a monoglyceride by thin layer chromatography. It resembled the unidentified lipid in that it had a high specific activity, exhibited differential activity, was inhibited by Staphylococcus aureus delta toxin, lecithin and Ca++, and its activity was reduced by oxidation. Stimulation of monoglyceride production by calcium ionophore requires the joint presence of components from the sedimented and supernatant fractions of abscess homogenates, and was not produced if boiled homogenate was used. The addition of verapamil interfered with the production of monoglyceride in homogenates treated with calcium ionophore. Monoglyceride was produced only in abscess homogenates and not in homogenates of other normal tissues or tissues taken from mice infected with S. aureus. Calcium ionophore could be replaced by inositol triphosphate, suggesting that monoglyceride production involved the release of calcium from intracellular stores. The 2-monoglyceride was the form originally produced in abscess homogenates, but this spontaneously isomerized to the 1-monoglyceride. The fatty-acid moiety of the monoglyceride consisted primarily of 16:0 and 16:1 fatty acids.

Topics: Abscess; Acyltransferases; Animals; Ascitic Fluid; Calcimycin; Calcium; Dose-Response Relationship, Drug; Female; Glycerides; Inositol Phosphates; Mice; Mice, Inbred ICR; Staphylococcal Infections; Staphylococcus aureus; Tissue Distribution

Available data indicate that B cell proliferation is inhibited in chronic renal failure and this is due to excess blood levels of PTH. This defect may also affect immunoglobulin production. We examined production of IgG, IgM and IgA by B cells stimulated with Staphylococcus aureus Cowan I (SAC) or with pokeweed mitogen (PWM) after eight days of culture and evaluated the effect of PTH on this process in 34 hemodialysis patients and 44 normal subjects. IgG, IgM and IgA production by B cells from patients was lower (P less than 0.01) than by B cells from normal subjects. Both 1-34 and 1-84 PTH inhibited (P less than 0.01) immunoglobulin production by B cells from normal subjects and dialysis patients. However, this inhibitory effect was evident in dialysis patients only with the higher dose of PTH. The inhibition of immunoglobulin production by PTH occurred only when the hormone was added at the initiation of the B cell culture. Inactivation of PTH abolished its inhibitory effect on immunoglobulin production. Agents that stimulate cAMP production (forskolin, cholera toxin) and the cAMP analogue, 8-bromoadenosine 3',5' cyclic monophosphate inhibited immunoglobulin production by B cells from both normal and dialysis patients, and the degree of inhibition was not different between the two groups. The calcium inophore A23187 also inhibited IgG, IgA and IgM production by B cells from normal subjects and dialysis patients; there was no significant difference in the degree of inhibition between the two groups. The resting levels of cytosolic calcium in B cells of dialysis patients was significantly (P less than 0.01) higher than that of B cells from normal subjects. The data show that: (1) immunoglobulin production is impaired in dialysis patients; (2) B cells of dialysis patients have elevated resting levels of cytosolic calcium; (3) PTH inhibits IgG, IgA and IgM production and this effect is at least partly mediated by PTH-induced cAMP production and alterations in cytosolic calcium into B cells; (4) this inhibitory effect is mediated by events that affect initial stages of B cell proliferation and maturation; (5) the requirement for high dose of PTH for its inhibitory effect on B cells from dialysis patients is probably due to desensitization and/or down-regulation of PTH receptors on B cells. The results are consistent with the proposition that impaired immunoglobulin production by B cells from dialysis patients is at least partly due to the state of secondary

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adult; Antibody Formation; B-Lymphocytes; Calcimycin; Calcium; Cholera Toxin; Colforsin; Female; Humans; Immunoglobulins; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Pokeweed Mitogens; Staphylococcal Infections

Histamine release from human basophil leukocytes was triggered by Staph. aureus, Salmonella enteritidis, non-haemolytic streptococci, or E. coli. Influenza A virus was found to enhance the mediator release and the effect was caused by synergism, since the virus did not induce release of histamine per se. This potentiating effect of the virus was seen both when the bacteria-induced histamine release was IgE-dependent (i.e. patient sensitized to the bacterium) and when the bacterium caused mediator release by a non-immunological mechanism independent of IgE (putative sugar-lectin mediated). Histamine release induced by anti-IgE and calcium ionophore or agarose-beads was also enhanced in the presence of the virus. These findings indicate that influenza A virus potentiates both IgE- and non-IgE-mediated histamine release induced by bacteria and other stimulators.

Topics: Bacterial Infections; Basophils; Calcimycin; Escherichia coli Infections; Histamine Release; Humans; Immunoglobulin E; In Vitro Techniques; Influenza A virus; Salmonella Infections; Staphylococcal Infections; Streptococcal Infections