Biomedical subjects

G M Ohlmann

Publications and source records attributed to G M Ohlmann.

6 recordsLinked to original sources

PubMed1986

Feline polymorphonuclear leukocytes respond chemotactically to leukotriene B4 and activated serum but not to F-Met-Leu-Phe.

The chemotactic response of feline polymorphonuclear leukocytes (PMNs) to three types of chemoattractants was studied. Feline PMNs responded to leukotriene B4 as well as to agarose-activated autologous and homologous serum. However, no response was obtained to N-formylmethionylleucylphenylalanine (FMLP), and four similar peptides that activate the FMLP receptor (N-formylnorleucylleucylphenylalanine, N-formylmethionylphenylalanine, methionylleucylphenylalanine, and pepstatin). Thus, feline PMNs are similar to equine, porcine, bovine and canine PMNs which also do not respond chemotactically to these peptides.

Animals↗

PubMed1986

The role of cyclooxygenase and lipoxygenase pathways in the adhesive interaction between bovine polymorphonuclear leukocytes and bovine endothelial cells.

The effects of arachidonic acid metabolites, analogues and cyclooxygenase/lipoxygenase inhibitors were tested on an "in vitro" bovine model of endothelial cell (EC)-polymorphonuclear leukocyte (PMN) adhesion. Arachidonic acid blocked adhesion at 10(-5)M, a dose which also induced aggregation of PMN. Lower doses did not affect either EC-PMN adhesion or PMN aggregation. Various cyclooxygenase pathway metabolites were inactive in the EC-PMN adhesion assay, with the exception of prostaglandin A2 and prostaglandin B2 which significantly suppressed adhesion at 10(-5)M. Of the synthetic analogs tested, 6 alpha-carbaprostacyclin I2, (5Z)-9 beta-ethynyl-calcium salt (U-64,567E) was inhibitory at 10(-5)M. The cyclooxygenase inhibitors acetylsalicylic acid, indomethacin and ibuprofen were inactive. Products of the lipoxygenase pathways, leukotriene B4 (LTB4), 5-hydroxyeicosatetraenoic acid (5-HETE) and 15-hydroperoxyeicosatetraenoic acid (15-HPETE) exhibited variable inhibitory activity at 10(-5)M only. Paradoxical effects were observed with the putative lipoxygenase inhibitors 4,7,10,13-eicosatetraynoic acid (4,7,10,13 ETYA), 5,8,11,14-eicosatetraynoic acid (5,8,11,14 ETYA) and nordihydroguairetic acid (NDGA), which also suppressed EC-PMN adhesion at 10(-5)M. The dual cyclooxygenase-lipoxygenase inhibitor, BW755C was inactive. Bovine PMNs did not respond chemotactically to LTB4 although they were able to synthesize the 5-lipoxygenase products LTB4 and 5-HETE.

Adhesiveness↗

PubMed1986

Countergradients of nonchemotactic ligands for N-formylmethionylleucylphenylalanine (FMLP) receptors promote FMLP-induced chemotaxis.

Using the under-agarose chemotaxis assay, addition of compounds known to inhibit chemotaxis of leukocytes toward N-f-Met-Leu-Phe (FMLP) was made to the first well in a line of three wells, leukocytes to the middle well, and a slight excess of FMLP to the third well. The compounds included rifampin, fusidic acid, carbobenzoxy Phe-Met, phenylbutazone, sulfinpyrazone, sulfasalazine, and sulfapyridine. The countergradients created in this system markedly stimulated, not inhibited, locomotion toward FMLP. These results, based on functional responses, confirm data using radiolabeled FMLP and support the hypothesis that these compounds are nonchemotactic ligands for FMLP receptors.

Binding, Competitive↗

PubMed1986

Antibiotic binding to human polymorphonuclear neutrophils, mouse leukemia L1210 cells and mouse thymocytes.

This report describes a system in which antibiotics could be compared for binding to different mammalian cells. These included functional phagocytes (human polymorphonuclear neutrophils; PMNs), non-phagocytic lymphocytes (mouse thymocytes), and non-functional leukocytes (mouse leukemia L1210 cells). When antibiotics bound to PMNs, they bound about the same to L1210 cells but much less to thymocytes. Combining these data with previous data, the ranking of cells that bound the greatest amount of antibiotics was: PMNs = L1210 cells = blood mononuclear leukocytes greater than thymocytes greater than erythrocytes. Thus, antibiotics bind differentially and not indiscriminately to mammalian cells.

Animals↗

PubMed1984

A simple system for studying antibiotic binding to leukocytes.

Studies on the interaction between antibiotics and polymorphonuclear leukocytes (PMLs) usually require the availability of radiolabeled antibiotic, that the antibiotic kill intraleukocyte pathogens, or that the antibiotic affect some function of the leukocyte. The system described here does not have the requirements above but depends instead upon anti-staphylococci activity. The key features of the system are that, following incubation, extracellular antibiotic was removed from PMLs by centrifugation, contact between Staphylococcus aureus 502A and the phagocyte-antibiotic complex was assured by centrifugation at 4 degrees C in 96 well tissue culture dishes, phagocytosis was induced by incubation at 37 degrees C, and assessment of surviving bacteria was accomplished by collecting [3H]thymidine labeled bacteria using a cell harvester. Antibiotics that were active in this system included naphthalenic ansamycins (rifamycins and streptovaricins ), lincosaminides ( clindamycins and pirlimycins ), coumarins (novobiocin), erythromycin, tetracycline, tyrocidine and paulomycin .

Anti-Bacterial Agents↗

PubMed1983

MIC values do not predict the intraphagocytic killing of Staphylococcus aureus by naphthalenic ansamycins.

Ten naphthalenic ansamycins were compared for their ability to kill extracellular or phagocytosed Staphylococcus aureus 502A. These included rifamycins, streptovaricins and tolypomycin Y. Although the compounds differed markedly in killing extracellular S. aureus, there was surprisingly little difference between them in assisting human leukocytes to kill phagocytosed S. aureus. In fact, when compared to rifampin, some ansamycins that were less effective in killing extracellular bacteria were more effective in killing phagocytosed bacteria. These data, together with an analysis of structure and activity, suggested that a specific transport mechanism might be involved. First considered was a vitamin K transport mechanism. Indeed warfarin, a vitamin K antagonist, blocked the ability of rifampin to kill phagocytosed S. aureus, as did the coumarins, novobiocin and coumarin-3-carboxylic acid. However, direct evidence for a vitamin K transport mechanism could not be obtained using vitamin K preparations. The fused phenolic, bicyclic system common to all of these ansamycins was tentatively considered to be the portion necessary for phagocyte penetration.

Anti-Bacterial Agents↗