Histamine releasing peptide (HRP) has proinflammatory effects and is present at sites of inflammation

Albumin, the most abundant plasma protein, readily enters sites of inflammation during the period of increased vascular permeability. There it encounters proteases released from mast cells and invading leukocytes which earlier work has shown can act on albumin to liberate the peptide, histamine releasing peptide (HRP), first identified and named by its ability to stimulate histamine release from isolated mast cells. In this report we show that HRP releases histamine from cutaneous mast cells in vivo resulting in increased vascular permeability and persistent edema while in vitro, HRP promotes chemotaxis of leukocytes and enhances macrophage phagocytosis. Moreover, we show that the level of HRP is increased with the induction of an acute cutaneous inflammatory response in rats, that HRP is present at sites of acute and chronic inflammation in humans and that HRP is rapidly degraded by proteases thereby limiting its action to the area of its generation. We suggest that HRP is a pro-inflammatory peptide that helps amplify and perpetuate the inflammatory response. Inhibitors of inflammatory proteases or antagonists that block the action of peptides like HRP may, therefore, be useful in breaking the cycle of inflammation.