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About 0.1% of the sera in human pathology produce a peculiar, cytoplasmic, non-organ- and non-species-specific fluorescence. This may easily be differentiated from the already described anti-organelle antibodies and, more particularly, from the mitochondrial antibodies of primary biliary cirrhosis. Should rat tissues he used in the immunofluorescence test, fluorescence predominates over the first two portions of the renal proximal tubules (P1 and P2) and the mucous neck cells of the stomach. This pattern may be attributed to mitochondria, and in particular to their inner membranes by fluorescent staining of the ellipsoid region of the rods and cones of the eyes, and by absorption with purified organelles. To distinguish this antibody from the already described mitochondrial antibodies, this one will be called mitochondrial antibody number 5 (M5). The seven carriers of this antibody suffer from systemic lupus erythematosus or autoimmune haemolytic anaemia. In these cases no diseases of the liver were observed, contrary to other classical mitochondrial antibodies. [ABSTRACT FROM AUTHOR]

We have compared the in-vitro interactions of quinine and cinchonine, two alkaloids from cinchona bark, with human neutrophil functions. Although these molecules are structurally similar, they induced a quantitatively different depressive effect on neutrophil chemotaxis and oxidative response. Quinine produced the strongest effect at concentrations as low as 10 mg/l, which may be achievable in serum during therapeutic use of this compound. The depression induced by cinchonine was noticeable only at 100 mg/l. Chemotaxis was decreased by about 25% (formyl-methionyl-leucyl-phenylalanine) or 39% (serum) for quinine (100 mg/l) only if a constant concentration of the drug was maintained during the assay while cinchonine had no effect on this PMN function. The greatest impairment was observed for the PMN oxidative burst: this was dose-dependent whatever the stimulus used (phorbol-myristate-acetate or opsonized zymosan). After 30 min incubation in the presence of the drugs, the zymosan-induced chemiluminescence response was decreased by 96% and by 67% with quinine, 100 and 10 mg/l, respectively, and by 62% with cinchonine 100 mg/l. The myeloperoxidase-mediated iodination of PMN was reduced by 100% and 46% with quinine, 100 and 10 mg/l, respectively, whereas cinchonine decreased this function by about 95% at 100 mg/l and 14% at 10 mg/l. Superoxide anion generation was impaired by 94% (quinine 100 mg/l) or 45% (cinchonine 100 mg/l). The relevance to the clinical situation and the possible mechanisms of such effects are discussed. [ABSTRACT FROM AUTHOR]

Josamycin, a 16-membered ring macrolide is concentrated up to 20-fold in phagocytic cells compared with serum. We have studied the in-vitro interaction of this drug with human neutrophils (PMN) bactericidal function by using two strains resistant to this antibiotic, Pseudomonas aeruginosa and Klebsiella pneumoniae, and a sensitive one, Staphylococcus aureus 209P. It was shown that josamycin-pretreated adherent PMN displayed an increased phagocytic activity (about 30 to 40%) for S. aureus or K. pneumoniae, mainly due to the recruitment of an additional phagocytizing subset of PMN. Furthermore, the bacterial killing was enhanced in josamycin-treated PMN in a dose-dependent manner for K. pneumoniae (60-130% increase in the range of concentration 0.1-25 mg/l) and independently of the dose for S. aureus (about 425-460% increase for josamycin 0.1-10 mg/l). P. aeruginosa killing by whole blood was also significantly increased in the presence of 10 and 1 mg/l of josamycin. Other PMN functions were not much altered by josamycin except an enhancement of the formyl-methionyl-leucyl-phenylalanine-induced oxidative response. Chemotaxis was only increased by the presence of a high concentration (100 mg/l) of josamycin. These data suggest that the bactericidal synergy between PMN and josamycin could be related, partly at least, to a direct enhancing effect of josamycin on some PMN functions such as phagocytosis, chemotaxis and FMLP-induced chemiluminescence. On the other hand, alterations of bacteria, either inside the phagolysosome or in the extracellular medium, could lead to an enhanced susceptibility to the phagocytes' microbial mechanisms. [ABSTRACT FROM AUTHOR]