EFFECTS OF SYNTHETIC PEPTIDO-LEUKOTRIENES ON BONE-RESORPTION IN-VITRO

Peptido-leukotrienes are short-lived organic molecules known to have p otent biological effects as mediators of inflammation, hypersensitivit y and respiratory disorders, However, little is known concerning their effects on bone cells, We have shown previously that stromal cells is olated from a human giant cell tumor secrete 5-HETE (5-hydroxyeicosate traenoic acid) and the peptido-leukotrienes, also known as the cystein yl leukotrienes LTC(4), LTD(4), and LTE(4). These eicosanoids,were sho wn to stimulate the multinucleated giant cells obtained from these tum ors to form resorption lacunae on sperm whale dentine, Here, we show t hat the peptido-leukotrienes also stimulate isolated avian osteoclast- like cells to form resorption lacunae and to increase their content of tartrate-resistant acid phosphatase. LTD(4) increased Ca-45 release f rom murine calvarial bone organ cultures, but not from fetal rat long bone cultures, Isolated avian osteoclast-like cells were chosen to per form receptor binding studies, as this population is the most homogeno us source of osteoclasts available. After the precursors had fused to form multinucleated cells, receptor binding assays were performed, Sca tchard analysis of saturation binding data showed a single class of bi nding sites, with a dissociation constant (K-d) of 0.53 nM and a recep tor density of 5,200 receptors per cell, Competition binding studies s howed receptor specificity using a specific LTD, receptor antagonist Z M 198,615, These data show that the peptido-leukotrienes activate high ly enriched populations of isolated avian osteoclast-like cells, and a lso that specific LTD(4) receptors are present in this cell population .