The immunomodulating agent RU 41740 complexed with very-low-density lipoproteins enhances human polymorphonuclear neutrophil oxidative metabolism in vitro.
Added to human serum in vitro, RU 41740, an immunomodulating agent extracted from Klebsiella pneumoniae, binds selectively to lipoproteins containing apolipoprotein B (low-density lipoproteins and very-low-density lipoproteins, VLDL) and, at higher concentrations, to lipoproteins containing apolipoprotein A (high-density lipoproteins). The fact that lipoproteins modulate polymorphonuclear neutrophil (PMN) functions led us to suspect that the VLDL-RU 41740 complex might affect PMN functions. In this study, the effect of this complex on PMN superoxide generation was measured in the presence and absence of the classical stimulants formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate. The VLDL-RU 41740 complex enhanced the stimulating effect of VLDL on quiescent PMN, but not following stimulation with formyl-methionyl-leucyl-phenylalanine. In contrast, it partially counteracted the inhibiting effect exerted by VLDL alone on phorbol myristate acetate stimulation. Such a complex might be formed in vivo during RU 41740 therapy and constitute an important feature in the immunostimulating properties of the drug.
Laboratoire de Pharmacologie et de Biochimie A, CNRS URA 595, Hôpital Cochin, Paris, France.
N
N
Idohou
R
R
Couderc
M
M
Roch-Arveiller
F
F
Tallet
J P
JP
Giroud
D
D
Raichvarg
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology*; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D008079:Lipoproteins, VLDL; D013481:Superoxides; C037567:glycoprotein, Klebsiella pneumoniae