Skin reactive factor and lymph node permeability factor

We have compared the properties of lymph node extracts from rat tissue with the properties of the supernatant obtained from the lectin-transformed rabbit peritoneal exudate lymphocytes in culture. Both extracts possess large amounts of lysosomal hydrolases, including particularly a cathepsin D-like protease. Both extracts are capable of increasing cutaneous permeability in the rat and causing a significant amount of cellular infiltration into the site of injection in the skin of these animals. This permeability-increasing activity and the cellular infiltration response to injection of these materials is completely inhibited by pepstatin and not by a variety of other inhibitors. Both extracts' permeability-increasing activity has a molecular weight range between 50,000 and 100,000 daltons and an isoelectric point of approximately 4.2. The molecular weight, the isoelectric point, and the inhibition by pepstatin are characteristic of cathepsin D from liver or spleen or granulocytes. Like cathepsin D, the permeability factor from LNPF and SRF extracts will release acid kinins from substrates which have been shown by Greenbaum and Houck to exist in the ground substance of rat skin. Finally, the breakdown products of the hydrolytic action of cathepsin D-like enzymes found in both lymph node extracts and supernatant from transformed lymphocytes are chemotactic for white blood cells. Thus, the two properties of cathepsin D described above, namely (a) the release of acid kinins which are capable of increasing the permeability of the microcirculation, and (b) the generation of chemotactic breakdown products via proteolysis could explain the two primary biological effects of both lymph node permeability factor and skin reactive factor.