title: Alpha 1-proteinase inhibitor is a neutrophil chemoattractant after proteolytic inactivation by macrophage elastase.
abstract: Mouse macrophage elastase, a metalloproteinase, catalytically inactivates human alpha 1-proteinase inhibitor (alpha 1-PI) by attacking a single peptide bond between Pro357 and Met358, resulting in Mr = 4,200 and 47,800 fragments. We show here that this proteolytically inactivated alpha 1-PI is a potent chemotactic factor for human neutrophils at a concentration of 1 nM. The chemotactic response is equivalent to that elicited by formyl-methionyl-leucyl-phenylalanine. Native alpha 1-PI does not stimulate chemotaxis. Purification of the two fragments of alpha 1-PI that result from proteolysis by macrophage elastase indicated that the Mr = 4,200 fragment is responsible for the chemotactic activity. However, the two proteolysis fragments do not dissociate from each other under physiologic conditions. Therefore, the ability of proteolytically inactivated alpha 1-PI to act as a mediator of inflammation is due to rearrangement of the alpha 1-PI molecule rather than to release of a cleavage fragment.
authors.affiliation: Laboratory of Radiobiology and Environmental Health, University of California, San Francisco 94143.
authors.forename: M J
authors.initials: MJ
authors.lastname: Banda
authors.forename: A G
authors.initials: AG
authors.lastname: Rice
authors.forename: G L
authors.initials: GL
authors.lastname: Griffin
authors.forename: R M
authors.initials: RM
authors.lastname: Senior
mesh_terms: D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D008970:Molecular Weight; D010196:Pancreatic Elastase / Q000378:metabolism*; D000515:alpha 1-Antitrypsin
chemical_list: D001798:Blood Proteins; D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase