Biological characterization of the enantiomeric hetrazepines of the paf-antagonist web 2170

Heuer, H.; Birke, F.W.; Brandt, K.; Muacevi, G.; Weber, Karl‐Heinz

doi:10.1016/0090-6980(88)90257-2

Cited by 12 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, WEB 2086 has been shown to counteract PAF-induced platelet aggregation competitively, since Schild plot slopes were not significantly different from unity and WEB 2086 shifted PAF-induced aggregation to the right in a parallel and concentration-dependent manner using platelets from various sources [51, 61,63,66]. Also for WEB 2170 (Ida), specific inhibition of PAF-induced platelet aggregation, at least at the same magnitude as for WEB 2086 has been shown (ICso values 0.3 and 0.03 pM, respectively) [39,68,69]. The same is true for the competition of…”

Section: Antagonism Of Exogenous Paf-induced Effects On Different Celmentioning

confidence: 93%

“…[3H]PAF binding to the PAF receptor on washed human platelets (Ki = 14 and 22 nM, respectively) [39]. The hetrazepine etizolam (12a) antagonized PAF-induced platelet aggregation (ICso = 3.8 pM in PRP from the rabbit) and inhibited the specific binding of [3H]PAF to the PAF receptor site on washed rabbit platelets [70].…”

Section: Antagonism Of Exogenous Paf-induced Effects On Different Celmentioning

confidence: 98%

“…With the aid of semipreparative high-performance liquid chromatography (HPLC) on a chiral phase WEB 2170 has been separated into its optical isomers. Table VIII summarizes the properties of both enantiomers [39].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Hetrazepines as antagonists of platelet activating factor

Weber

Heuer

1989

Medicinal Research Reviews

View full text Add to dashboard Cite

Section: Antagonism Of Exogenous Paf-induced Effects On Different Celmentioning

confidence: 93%

Section: Antagonism Of Exogenous Paf-induced Effects On Different Celmentioning

confidence: 98%

See 1 more Smart Citation

Hetrazepines as antagonists of platelet activating factor

Weber

Heuer

1989

Medicinal Research Reviews

View full text Add to dashboard Cite

“…The final ethanol concentration in the experiments did not exceed 1%. WEB 2170, a specific PAF receptor antagonist, was from Boehringer-Ingelheim (Munich, Germany) [22].…”

Section: Lipids and Reagentsmentioning

confidence: 99%

Lysophosphatidylcholine (LPC) induces proinflammatory cytokines by a platelet-activating factor (PAF) receptor-dependent mechanism

Huang

Elinder

et al. 1999

Clinical and Experimental Immunology

170

137

View full text Add to dashboard Cite

Oxidized low-density lipoprotein (oxLDL) consists of both lipid components and apoprotein B100. OxLDL has both proinflammatory and cytotoxic properties. The present study was undertaken to investigate the effects of components in the lipid moiety of oxLDL on immune activation as determined by cytokine and immunoglobulin secretion. LPC induced interferon-gamma (IFN-gamma) secretion in peripheral blood mononuclear leucocytes from healthy blood donors. The effect varied between individuals, and there were both responders and non-responders. Furthermore, LPC induced enhanced antibody production, indicating B cell activation. None of eight oxysterols, arachidonic acid (AA), or 15-lipoxygenase products of AA tested had immune stimulatory properties. We recently demonstrated that PAF and oxLDL induce IFN-gamma secretion by a common mechanism. LPC-induced IFN-gamma secretion was inhibited by a specific PAF receptor antagonist, WEB 2170, indicating that the PAF receptor is involved in LPC-induced immune activation. Both oxLDL- and LPC-induced antibody formation was inhibited by WEB 2170. Furthermore LPC also induced tumour necrosis factor-alpha secretion, and this effect was inhibited by WEB 2170. LPC is produced during lipid oxidation (as in oxLDL), but also by enzymes such as phospholipase A2. The findings indicate that LPC may play an important role in inflammatory reactions, including atherosclerosis.

show abstract

“…A specific PAF-receptor antagonist, WEB 2170 [16], was a kind gift from Boehringer-Ingelheim (Ingelheim, Germany).…”

Section: Lipidsmentioning

confidence: 99%

Induction of IL-4 by platelet-activating factor

Huang

Elinder

Owman

et al. 1996

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYPlatelet-activating factor (PAF) is a phospholipid inflammatory mediator which is synthesized by a variety of cells, including monocytes, endothelial cells, mast cells and neutrophils. PAF acts via a recently cloned PAF receptor, present on monocytes and endothelial cells, but not on non-activated lymphocytes. IL-4 is mainly produced by T lymphocytes, and belongs to the Th2 subset of T helper cells. IL-6 is mainly a monocyte/macrophage-derived cytokine with multiple proinflammatory effects. We here report that PAF induces IL-4 production, as determined by ELISPOT. Antibodies to MHC class II inhibited the IL-4 stimulatory effects of PAF. PAF also had the capacity to induce IgA production, as determined by ELISPOT, and IL-6 production in peripheral blood mononuclear cells (PBMC) as determined by ELISA. These PAF-mediated effects were completely inhibited by a specific PAFreceptor antagonist, WEB 2170. Taken together, our data indicate that PAF activates T lymphocytes to IL-4 production by an indirect, monocyte-dependent mechanism dependent on MHC class II. PAF also enhances antibody formation and IL-6 production from PBMC. These findings indicate that PAF activates immune-competent cells, which may be of importance in inflammatory diseases such as asthma, vasculitis and atherosclerosis.

show abstract

Biological characterization of the enantiomeric hetrazepines of the paf-antagonist web 2170

Cited by 12 publications

References 0 publications

Hetrazepines as antagonists of platelet activating factor

Hetrazepines as antagonists of platelet activating factor

Lysophosphatidylcholine (LPC) induces proinflammatory cytokines by a platelet-activating factor (PAF) receptor-dependent mechanism

Induction of IL-4 by platelet-activating factor

Contact Info

Product

Resources

About