EFFECT OF ROXITHROMYCIN ON PHAGOCYTOSIS-CONNECTED OXYGEN CONSUMPTION AND OPSONIZING ACTIVITY IN WHOLE BLOOD

The modulation of host antimicrobial activity by antibiotics is of therapeutic importance. The effect of serum on drug activity is also of clinical interest. We studied the effect of roxithromycin on the opsonizing time of plasma and the oxygen consuming activity of phagocytes in peripheral whole blood that reflects in vivo bacteremia more than isolated serum and granulocytes. Roxithromycin has no effect on the opsonizing activity at any concentrations we examined. At lower concentration (<50μg/ml), roxithromycin does not give any effects on zymosan-stimulated oxygen consumption either. At the highest concentration (200μg/ml) we examined, the antibiotic however decreases it to the extent comparable to that reported in serum-free reconstituted in vitro system. These results indicate that roxithromycin has modulatory effects neither on anti-microbial oxygen metabolism of phagocytes nor on the opsonizing activity of plasma at pharmacological concentration, but is inhibitory on the former at its toxic concentration. On the other hand, serum proteins have no effects on drug toxicity in this context in comparison to in vitro studies (24, 30)

cDNA cloning and sequencing of component C5 of proteasomes from rat hepatoma cells

AbstractProteasomes are multicatalytic proteinase complexes consisting of a set of non-identical polypeptide subunits. A cDNA for component C5 of rat proteasomes was isolated by screening a Reuber H4TG hepatoma cell cDNA library using synthetic oligodeoxynucleotide probes corresponding to partial amino acid sequences of the protein. The polypeptide deduced from the open reading frame consisted of 240 amino acid residues with a calculated molecular weight of 26479. Computer analysis revealed little similarity of C5 to other proteins reported so far. The primary structure of C5 showed partial sequence homology to that of another component C3, but no regions of homology with the sequence of component C2. Thus C5 is concluded to be a new type of subunit of the proteasome complex

Increased phagocytosis of platelets from patients with secondary dengue virus infection by human macrophages.

The relationship between the percent phagocytosis of platelets by differentiated THP-1 cells was examined using flowcytometry and the peripheral platelet counts as well as platelet-associated IgG (PAIgG) in 36 patients with secondary dengue virus (DV) infections. The percent phagocytosis and the levels of PAIgG were significantly increased in these patients during the acute phase compared with the healthy volunteers. The increased percent phagocytosis and PAIgG found during the acute phase significantly decreased during the convalescent phase. An inverse correlation between platelet count and the percent phagocytosis (P = 0.011) and the levels of PAIgG (P = 0.041) was found among these patients during the acute phase. No correlation was found, however, between the percent phagocytosis and the levels of PAIgG. Our present data suggest that accelerated platelet phagocytosis occurs during the acute phase of secondary DV infections, and it is one of the mechanisms of thrombocytopenia in this disease

Critical roles of interferon regulatory factor 4 in CD11b(high)CD8α(–) dendritic cell development

IFN regulatory factors (IRFs) are a family of transcription factors that play an essential role in the homeostasis and function of immune systems. Recent studies indicated that IRF-8 is critical for the development of CD11b(low)CD8α(+) conventional dendritic cells (DCs) and plasmacytoid DCs. Here we show that IRF-4 is important for CD11b(high)CD8α(–) conventional DCs. The development of CD11b(high) DCs from bone marrow of IRF-4(–/–) mice was severely impaired in two culture systems supplemented with either GM-CSF or Flt3-ligand. In the IRF-4(–/–) spleen, the number of CD4(+)CD8α(–) DCs, a major subset of CD11b(high) DCs, was severely reduced. IRF-4 and IRF-8 were expressed in the majority of CD11b(high)CD4(+)CD8α(–) DCs and CD11b(low)CD8α(+) DCs, respectively, in a mutually exclusive manner. These results imply that IRF-4 and IRF-8 selectively play critical roles in the development of the DC subsets that express them