[Proteins of the inter-alpha trypsin inhibitor (ITI) family. A major role in the biology of the extracellular matrix].
A glycoprotein with a high inhibitory activity against trypsin was isolated in 1961 from human plasma and named inter-alpha trypsin inhibitor (ITI). Since then, several other proteins that share antigenic and structural similarities with ITI have been identified and classified as members of the ITI protein family. These glycoproteins built up from different combinations of four polypeptides HC1, HC2, HC3 and bikunin are encoded by four genes H1, H2, H3, L on three chromosomes. Bikunin has two proteinase inhibitor domains and belongs to the Kunitz-type protease inhibitor family; it displays an inhibitory activity against trypsin, leukocyte elastase and plasmin. The heavy chains do not have any protease inhibitory properties but have the capacity to interact in vitro and in vivo with hyaluronic acid. This binding promotes the stability of the extra-cellular matrix. Consequently, the ITI protein family is suspected of playing a key role in the extra-cellular matrix biology. Isolation of free heavy chains in bronchial secretions and the recent emphasis about the bikunin role in tumoral invasion should enhance the interest about ITI protein family in the pathophysiology of chronic bronchopulmonary diseases or lung cancer progression.
Cuvelier
A
A
Unité INSERM 295, CHU de Rouen. antoine.cuvelier@chu-rouen.fr
Muir
J F
JF
Martin
J P
JP
Sesboüé
R
R
D000933:Antifibrinolytic Agents / Q000494:pharmacology; D001695:Biology; D005109:Extracellular Matrix / Q000201:enzymology*; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D008173:Lung Diseases, Obstructive / Q000503:physiopathology; D008175:Lung Neoplasms / Q000503:physiopathology; D008562:Membrane Glycoproteins; D011485:Protein Binding; D015842:Serine Proteinase Inhibitors / Q000145:classification / Q000235:genetics / Q000502:physiology*; D014360:Trypsin Inhibitor, Kunitz Soybean; D014361:Trypsin Inhibitors / Q000502:physiology; D000515:alpha 1-Antitrypsin / Q000145:classification / Q000235:genetics / Q000502:physiology*
D000933:Antifibrinolytic Agents; D006023:Glycoproteins; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin; D006820:Hyaluronic Acid; D014360:Trypsin Inhibitor, Kunitz Soybean; D019272:Leukocyte Elastase
Les protéines de la famille de l'ITI (inter-alpha trypsine inhibiteur). Un rôle majeur dans la biologie de la matrice extra-cellulaire.