The anionic amphiphile SDS is an antagonist for the human neutrophil formyl peptide receptor 1.
The anionic amphiphil sodium dodecyl sulfate (SDS) is commonly used to activate the superoxide-generating NADPH-oxidase complex in cell-free systems, but very little is known about the effects of SDS on intact cells. It was, however, recently shown that SDS causes a translocation and an activation of Rac (a small G-protein) in intact cells, but this signal is not in its own sufficient to activate the oxidase (Nigorikawa et al. (2004) [1]). We found that SDS acted as an antagonist for FPR1, one of the neutrophil members of the formyl peptide receptor family. Accordingly, SDS reduced superoxide anion production induced by the chemoattractant formylmethionyl-leucyl-phenylalanine (fMLF). The receptor specificity of SDS was fairly high, but the concentration range in which it worked was narrow. The length of the carbohydrate chain as well as the charge of the molecule was of importance for the antagonistic effects. Signaling through FPR2, a closely related receptor also expressed in neutrophils, was not inhibited by SDS. On the contrary, the response induced by the FPR2-specific agonist WKYMVM was primed by SDS. The precise mechanism behind the primed state is not known, but might be related to the effects earlier described for SDS on the small G-protein Rac, that is of importance for a proper transduction of the down-stream signals from the occupied receptor.
Thorén
Fredrik B
FB
Department of Clinical Virology, Göteborg University, Guldhedsgatan 10, S-413 46 Göteborg, Sweden.
Karlsson
Jennie
J
Dahlgren
Claes
C
Forsman
Huamei
H
D000838:Anions; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry / Q000494:pharmacology*
D000838:Anions; C469986:FPR1 protein, human; D044042:Receptors, Formyl Peptide; D012967:Sodium Dodecyl Sulfate