Heparin increases hillock formation in mesangial cell cultures

Mesangial cells in culture develop hillocks, which are composed of aggregates of cells, necrotic cellular debris, and extracellular matrix material. The significance and mechanism of their formation are unknown. To determine whether a proliferative component is involved in hillock formation, cells were treated with heparin or irradiated to inhibit proliferation. Heparin caused a 50% inhibition of mesangial cell growth and stimulated hillock formation three-fold to fourfold. Irradiated cells developed hillocks to the same extent as did nonirradiated cells, and the addition of heparin also increased hillock formation threefold to fourfold. Dextran sulfate and chondroitin B sulfate had no effect on mesangial cell hillock formation. Mesangial cells cultured in the presence of 50 micrograms/mL of heparin were less tightly adhered than nontreated cells, as assessed by a trypsin adhesion assay (control cells, 12% detached; heparin-treated cells, 72% detached). Thus, it appears that heparin, a glycosaminoglycan with potent antimitogenic activity, stimulates mesangial cell hillock formation, possibly by decreasing cell adhesion.