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- Title
Acute-Phase Protein α1-Antitrypsin Inhibits Neutrophil Calpain I and Induces Random Migration.
- Authors
Al-Omari, Mariam; Korenbaum, Elena; Ballmaier, Matthias; Lehmann, Ulrich; Jonigk, Danny; Manstein, Dietmar J.; Welte, Tobias; Mahadeva, Ravi; Janciauskiene, Sabina
- Abstract
A rapid recruitment of neutrophils to sites of injury or infection is a hallmark of the inflammatory response and is required for effective host defense against pathogenic stimuli. However, neutrophil-mediated inflammation can also lead to chronic tissue destruction; therefore, a better understanding of the mechanisms underlying neutrophil influx and activation is of critical importance. We have previously shown that the acute phase protein α1-antitrypsin (AAT) inhibits neutrophil chemotaxis. In this study, we examine mechanisms related to the effect of AAT on neutrophil responses. We report a previously unknown function of AAT to inactivate calpain I (μ-calpain) and to induce a rapid cell polarization and random migration. These effects of AAT coincided with a transient rise in intracellular calcium, increase in intracellular lipids, activation of the Rho GTPases, Rac1 and Cdc42, and extracellular signal-regulated kinase (ERK1/2). Furthermore, AAT caused a significant inhibition of nonstimulated as well as formyl-metleu- phe (fMLP)-stimulated neutrophil adhesion to fibronectin, strongly inhibited lipopolysaccharide-induced IL-8 release and slightly delayed neutrophil apoptosis. The results presented here broaden our understanding of the regulation of calpain-related neutrophil functional activities, and provide the impetus for new studies to define the role of AAT and other acute phase proteins in health and disease.
- Subjects
ACUTE phase proteins; TRYPSIN inhibitors; NEUTROPHILS; INFLAMMATORY mediators; CALPAIN
- Publication
Molecular Medicine, 2011, Vol 17, Issue 9/10, p865
- ISSN
1076-1551
- Publication type
Article
- DOI
10.2119/molmed.2011.00089