SOLUBLE CD14 FROM URINE COPURIFIES WITH A POTENT INDUCER OF CYTOKINES

Here we report that soluble CD14 isolated from the urine of nephrotic patients (uCD14) contains a potent cytokine inducing activity. CD14 de rived from urine appeared to consist of two major polypeptides of abou t 54 and 48 kDa. In uCD14 isolated from three different nephrotic pati ents the cytokine-inducing activity appeared to co-migrate with the 48 -kDa polypeptide which upon sequencing had the same N-terminal sequenc e as native CD14. Treatment of human monocytes and the human astrocyto ma cell line U373 with uCD14 resulted in a strong secretion of tumor n ecrosis factor (TNF) and interleukin-6, respectively. The cytokine-ind ucing activity of the uCD14 preparations was unaffected by the absence of serum. This is in contrast to the activation of human monocytes an d U373 cells by lipopolysaccharide (LPS) which is highly dependent on the presence of serum. The cytokine-inducing activity was not affected by LPS-binding protein (LBP) or polyclonal rabbit antibodies against LBP. The TNF-inducing activity of uCD14 was also heat labile in contra st to the cytokine-inducing activity of LPS, which was relatively heat resistant. The results suggest that CD14 may exist in at least two fo rms of which one is involved in cytokine induction.