[Pharmacologic remobilization of hyperadhesive granulocytes: a new principle in "anti-inflammatory" therapy].
It is thought that the nonsteroidal anti-inflammatory drugs act through inhibition of cyclooxygenase (CO). The authors show that the pyrazolon derivatives phenylbutazone (P) and sulfinpyrazone (S) affect PMN function in a manner independent of CO inhibition. During inflammation PMN often show increased adhesiveness. Such adhesiveness can be provoked in vitro by high concentrations of chemotaxins. Preincubation (10--20 minutes) of platelet-free human PMN suspensions in heat-inactivated plasma with 100 micrograms P or S per ml completely abolished a submaximal adherence induction on Petri dishes from 4% adherent cells in the absence, to 23% in the presence, of 10(-7) M of the chemotaxin N-f-Met-Leu-Phe (FP). In vivo, premedication of rabbits with P or S prevented the FP-induced neutropenia, e.g. 10 mg/kg of S blocked a 5-minutes agranulocytosis. P and S also abrogated adherence-induced lysosomal enzyme release and FP-stimulated hexose monophosphate pathway (HMP) activity. FP-induced hyperadhesiveness impedes PMN locomotion. Preincubation of PMN with P or S reestablished random motility and allowed chemotactic migration toward activated C (as C5a) in spite of the presence of 'adhesive' concentrations of FP. The potent CO inhibitors indomethacin and aspirin had no effect on FP-induced adherence, enzyme release, neutropenia and HMP stimulation. In 3 selected patients with PMN hyperadhesiveness, correction of this adhesiveness by P paralleled clinical remission. It is concluded that P and S exert their antiinflammatory action at least in part by interfering with PMN hyperadhesiveness and lysosomal enzyme release. These effects are independent of the prostaglandin-thromboxane system, since other CO inhibitors are uneffective.
D002448:Cell Adhesion / Q000187:drug effects*; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D009504:Neutrophils / Q000187:drug effects*; D010653:Phenylbutazone / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D013442:Sulfinpyrazone / Q000494:pharmacology
D011720:Pyrazoles; D010653:Phenylbutazone; D013442:Sulfinpyrazone
Pharmakologische Remobilisation von hyperadhärenten Granulozyten: ein neues Prinzip in der "antiinflammatorischen" Therapie.