Hyaluronic acid accumulation; the mechanism behind graft rejection edema.

Hyaluronic acid (HA) is an important stabilizing consistuent of the loose connective tissue and regulates water homeostasis. Thus, excessive accumulation of HA in interstitial tissue immobilizes water and may thereby contribute to interstitial tissue edema. By the use of biotin labelled core protein and an avidin-enzyme system, we visualized HA in grafted rat kidney, rat heart, rat small bowel and also in human kidneys. By an extraction procedure the tissue amounts of HA were measured in the experimental grafts. Simple techniques for measuring water content were also employed. The extracellular amounts of HA increased between 100% and 350% in rejecting tissues as compared to syngeneic controls. The relative water content also increased and correlated well with the HA accumulation. The clinical value of these experimental observations was confirmed in human transplantation where rejecting kidney allografts demonstrated a highly significant increase in HA staining in the interstitium as compared to non-rejecting biopsy specimens. We therefore concluded that transplantation edema--a key features of graft rejection--is regulated by the accumulation of HA not only under experimental conditions but also in the clinical setting.