Interactions between alkylglycerols and human neutrophil granulocytes.
We evaluated whether various alkylglycerols would initiate a functional response of human neutrophils or modify responses induced by a formyl peptide (fMLP) in vitro. We found that platelet activating factor (PAF) was the most potent with regard to the ability to produce an oxidative response (assessed by cytochrome c reduction and/or chemiluminescence), followed by ET-16-OCH3. Lyso-PAF, ET-18-OCH3, batyl- and chimyl alcohols exhibited only a weak activity. PAF was also the most efficient lipid conferring a rise of intracellular calcium concentrations ([Ca2+]i). ET-16-OCH3, ET-18-OCH3 and lysoPAF were less potent, although maximal [Ca2+]i levels were similar to that of 0.1 mumol/l fMLP. The kinetics of the calcium responses were highly specific for each ether lipid. When neutrophils had been treated with PAF or ET-18-OCH3 and were subsequently stimulated by fMLP, enhancement of the oxidative response was noted. Thus, this study shows that there was an association between the ability of an alkylglycerol to initiate oxidative and calcium responses, indicating strict structure-activity relationships for these lipids.
Palmblad
J
J
Department of Medicine III, Karolinska Institute, Stockholm, Sweden.
Samuelsson
J
J
Brohult
J
J
D002118:Calcium / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D005995:Glyceryl Ethers / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology
D003574:Cytochrome c Group; D005995:Glyceryl Ethers; C029271:O-deacetyl platelet activating factor; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C026659:edelfosine; C033433:batyl alcohol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium; C004348:chimyl alcohol