The inter-(alpha) trypsin inhibitor (ITI) family is a group of structurally related plasma serine protease inhibitors synthesized in the liver and built up from different combinations of three highly homologous heavy chains (ITI-HI, ITI-H2 and ITI-H3) and one light chain (bikunin). A fourth member of the ITI family, ITI-H4 (also known as I (alpha) IH4P) harbours a Pro-rich region (PRR) in its c-terminus. ITI (also known as IaI) is a 220 kDa glycoprotein composed of three polypeptides linked by chondroitin sulphate: two heavy chains, ITI-H1 (65 kDa) and ITI-H2 (72 kDa), and bikunin (approx. 30 kDa). Bikunin confers the protease-inhibitor function of ITI. The heavy chains of the ITI family, designated as SHAPs (for serum-derived hyaluronan-associated proteins), bind
covalently to hyaluronic acid (HA), resulting in pericellular matrix stabilization. ITI-H1 contains a potential peptide which could stimulate a broad spectrum of phagocytotic cells.