Human monocyte-derived insulin-like growth factor-2 enhances the infectionof human arterial endothelial cells by Chlamydia pneumoniae

It has been shown that infection of human endothelial cells by Chlamydia pn eumoniae is enhanced by co-culturing endothelial cells with human monocytes and is mediated by monocyte-derived soluble factors. This study was conduc ted to identify the infectivity-enhancing factor. Serum-free conditioned me dium of human monocytic cells was fractionated by ultrafiltration. The enha ncing activity was found in the fraction in the molecular mass range betwee n 5000 and 10,000 kDa. Recombinant human insulin-like growth factor (IGF)-1 or -2, with a molecular mass of 7500 kDa, was added to the culture medium of human endothelial cells for growing C. pneumoniae. Only IGF-2 enhanced C . pneumoniae growth. Pretreatment of the conditioned medium with a monoclon al antibody against IGF-2 blocked the enhancing activity. This suggests tha t the infectivity-enhancing factor is IGF-2 and that paracrine interactions between monocytes and endothelial cells in vivo can induce secretory produ cts and sustain infection with C. pneumoniae within atherosclerotic lesions .