Alpha-1 Antitrypsin Deficiency: Pathogenesis, Clinical Presentation, Diagnosis, and Treatment

Köhnlein, Thomas; Welte, Tobias

doi:10.1016/j.amjmed.2007.07.025

Cited by 126 publications

(98 citation statements)

References 38 publications

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“…Current knowledge clearly indicates that diverse APPs regulate neutrophil activities. For example, α1-antitrypsin (AAT)-which is an archetypal member of the SERPIN superfamily, a main inhibitor of neutrophil elastase (2) and an α1 acid glycoprotein, a member of the lipocalin family, carrying hydrophobic molecules (3)-inhibits formyl-met-leu-phe (fMLP) or interleukin (IL)-8-induced neutrophil activation, chemotaxis and adhesion; induces macrophage-derived IL-1 receptor antagonist release; and protects mice from endotoxin-induced septic shock (4)(5)(6)(7)(8)(9)(10). Similarly, C-reactive protein (opsonin) and haptoglobin (hemoglobin binder) inhibit neutrophil chemotaxis, superoxide production and degranulation (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Acute-Phase Protein α1-Antitrypsin Inhibits Neutrophil Calpain I and Induces Random Migration

Al-Omari

Korenbaum

Ballmaier

et al. 2011

Mol Med

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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.

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Section: Introductionmentioning

confidence: 99%

Acute-Phase Protein α1-Antitrypsin Inhibits Neutrophil Calpain I and Induces Random Migration

Al-Omari

Korenbaum

Ballmaier

et al. 2011

Mol Med

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“…Severe deficiency of a 1 -antitrypsin is seen with the PiZZ genotype, which leads to the clinical manifestations of emphysema, cirrhosis, and panniculitis. 11, 12 The latter presents as recurrent ulcerating subcutaneous nodules precipitated by trauma, and it may precede other clinical stigmata of the disease.…”

Section: Pancreatic Panniculitismentioning

confidence: 99%

Neutrophilic Panniculitis: Algorithmic Approach to a Heterogeneous Group of Disorders

Chan

2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.—Neutrophilic panniculitis encompasses an etiologically and morphologically heterogeneous group of disorders. Correct histopathologic diagnosis is important in identifying certain systemic diseases and guiding appropriate treatment. Objective.—To review the clinical and histopathologic features of different types of neutrophilic panniculitis, and to provide a diagnostic algorithm for these disorders. Data Sources.—A review of the literature with emphasis on the distinguishing features of different entities was performed. Conclusions.—Evaluation for neutrophilic panniculitis entails paying close attention to the pattern of inflammation, the type of fat necrosis present, any evidence of vascular damage, and other relevant histopathologic features. An algorithmic approach integrating all histopathologic, clinical, and laboratory findings is required for correct diagnosis.

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“…Elevation of serum AAT, assessment and association of its phenotype and genotype with regard to specific type of cancer has been subject of many studies on different types of cancers such as gastrointestinal cancers, brain tumors, biliary tract cancer, pancreatic adenocarcinoma, cancers of the prostate, breast, lung and liver [22,23,[30][31][32]. Regarding esophageal cancer, there are limited reports available from Japan and Korea as well as our recent repot [21,33].…”

Section: Aat As a Tumor Marker And Its Clinical Applicabilitymentioning

confidence: 99%

Structural Features, Biological Functions of the Alpha-1 Antitrypsin and Contribution to Esophageal Cancer

Ganji¹,

Jazii²,

Sahebghadam-Lotfi³

2012

Squamous Cell Carcinoma

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Alpha-1 Antitrypsin Deficiency: Pathogenesis, Clinical Presentation, Diagnosis, and Treatment

Cited by 126 publications

References 38 publications

Acute-Phase Protein α1-Antitrypsin Inhibits Neutrophil Calpain I and Induces Random Migration

Acute-Phase Protein α1-Antitrypsin Inhibits Neutrophil Calpain I and Induces Random Migration

Neutrophilic Panniculitis: Algorithmic Approach to a Heterogeneous Group of Disorders

Structural Features, Biological Functions of the Alpha-1 Antitrypsin and Contribution to Esophageal Cancer

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