ABSTRACT
Members of the chemokine gene superfamily are known to play a central role in leukocyte extravasation; however, their involvement in acute inflammation in response to micro-organisms has not yet been well studied. We have therefore investigated the role of murine macrophage-inflammatory protein (muMIP) 1alpha and muMIP-2 in the inflammatory response mounted against the bacteria Salmonella enteritidis and the Sacchromyces cerevisiae cell wall component, zymosan. Leukocyte extravasation was monitored in murine s.c. air pouches. Both agonists induced accumulation of leukocytes in a dose- and time-dependent manner, with the response peaking after 4 h and declining thereafter. The inflammatory exudate comprised mainly neutrophils; however, an increase in eosinophil accumulation was also observed in response to zymosan. The production of both muMIP-1alpha and muMIP-2 increased with time in response to both the agonists, although production was more sustained in response to the bacteria. Prior treatment of mice with neutralizing Abs against muMIP-1alpha or muMIP-2, either alone or in combination, failed to attenuate the accumulation of leukocytes in response to the agonists. In contrast, the anti-muMIP-2 Abs significantly inhibited leukocyte recruitment in response to S. enteritidis in complement-deficient mice. Taken together, these data show that while muMIP-1alpha and muMIP-2 are produced in response to phagocytosis of micro-organisms in s.c. tissue, under these circumstances components of the complement pathway appear to play a dominant role in the recruitment of neutrophils.
Subject(s)
Chemokines/biosynthesis , Saccharomyces cerevisiae/immunology , Salmonella enteritidis/immunology , Animals , Buffers , Cell Movement/immunology , Chemokine CCL4 , Chemokine CXCL2 , Chemokines/antagonists & inhibitors , Chemokines/immunology , Complement C5/deficiency , Complement C5/genetics , Diffusion Chambers, Culture , Down-Regulation/genetics , Down-Regulation/immunology , Exudates and Transudates/cytology , Exudates and Transudates/immunology , Exudates and Transudates/metabolism , Exudates and Transudates/microbiology , Female , Immune Sera/administration & dosage , Injections, Intraperitoneal , Injections, Subcutaneous , Macrophage Inflammatory Proteins/biosynthesis , Male , Mice , Mice, Inbred BALB C , Mice, Mutant Strains , Phagocytes/immunology , Phagocytosis/genetics , Phosphates/administration & dosage , Sodium Chloride/administration & dosage , Sodium Chloride/pharmacology , Zymosan/administration & dosageABSTRACT
A novel, potent and selective inhibitor of bacterial tyrosyl tRNA synthetase, designated SB-219383 has been isolated from Micromonospora sp. NCIMB 40684. The fermentation, isolation and some properties are described, whilst the structure determination is described in the succeeding paper). SB-219383 showed competitive, inhibitory activity against a Staphylococcus tyrosyl tRNA synthetase, with an IC50 of <1 nM, and exhibited weak in vitro activity against some Streptococcus sp.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/isolation & purification , Enzyme Inhibitors/isolation & purification , Furans/isolation & purification , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Chromatography, High Pressure Liquid , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Fermentation , Furans/chemistry , Furans/pharmacology , Microbial Sensitivity Tests , Micromonospora , Tyrosine-tRNA Ligase/antagonists & inhibitorsABSTRACT
The oriC transducing phage lambda poriCc is a pseudovirulent phage capable of forming plaques on a lambda lysogen. This phenotype is dependent upon the presence of the oriC insert. The ability of lambda poriCc to form plaques on a lambda lysogen represents a potential phage assay system for studying aspects of oriC function. In the present study we establish that lambda poriCc infection of a lambda lysogen is a legitimate assay for oriC function. We use this assay to confirm the previously reported observation that initiation of DNA replication from oriC is transiently inhibited in a ultra violet (UV) irradiated cell at doses greater than 60 J/m2. We further demonstrate using this assay that the UV induced inhibition of initiation of DNA replication from oriC is not a SOS function nor a heat shock function. In the course of these studies, we found that lambda poriCc infection of a non-lysogenic cell is extremely sensitive to pre-irradiation of the Escherichia coli host. We postulate that the sensitivity of lambda poriCc replication to host cell pre-irradiation reflects in some way the transient inhibition of initiation of DNA replication from oriC following UV irradiation.
Subject(s)
DNA Replication/physiology , DNA Replication/radiation effects , DNA-Binding Proteins/physiology , Escherichia coli/radiation effects , Viral Proteins/physiology , Bacteriophage lambda/genetics , Bacteriophage lambda/radiation effects , DNA-Binding Proteins/radiation effects , Escherichia coli/genetics , Heat-Shock Proteins/physiology , Membrane Proteins/physiology , Origin Recognition Complex , Son of Sevenless Proteins , Time Factors , Ultraviolet Rays , Viral Proteins/radiation effectsABSTRACT
SB-202742 [1], an anacardic acid derivative possessing beta-lactamase inhibitory activity, has been isolated from a hexane extract of the plant, Spondias mombin. Its isolation, structure determination, and biological activity are reported herein.
Subject(s)
Anacardic Acids , Plants/chemistry , Salicylates/isolation & purification , beta-Lactamase Inhibitors , Chromatography, High Pressure Liquid , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/enzymology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Conformation , Plant Extracts/pharmacology , Salicylates/pharmacologyABSTRACT
Two novel glycopeptide antibiotics MM 55266 and MM 55268 containing fatty acid acyl functions, and of molecular formula C86H89N8O35Cl5 and C87H91N8O35Cl5, respectively, have been isolated and identified from a complex produced by Amycolatopsis sp. NCIB 40089. Fermentation conditions for their production, and methods for their isolation are described. Structures have been deduced by use of COSY and NOE NMR techniques and supported by chemical degradation studies. Both glycopeptides possessed good antibacterial activity against Gram-positive organisms.
