The immunomodulating agent RU 41740 complexed with very-low-density lipoproteins enhances human polymorphonuclear...

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.