Cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Correlation to changes in the cytosolic free Ca2+ level and action of phorbol myristate acetate.

Andersson, Tommy; Dahlgren, Cláes; Lew, P D; Stendahl, Olle

doi:10.1172/jci112941

Cited by 65 publications

(39 citation statements)

References 43 publications

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“…The cells were washed and resuspended (10 7 /ml) in Krebs-Ringer phosphate buffer containing glucose (10 mM), Ca 2ϩ (1 mM), and Mg 2ϩ (1.5 mM) (KRG; pH 7.3). This procedure allows for cells to be isolated with minimal mobilization effects (1).…”

Section: Methodsmentioning

confidence: 99%

“…The amount of FPR on the cell surface was determined by incubating the neutrophils with radiolabeled fMLF in the presence or absence of excess unlabeled fMLF as described earlier (1). In short, 100 l of dibutylphthalate mixed with dinonylphthalate (10:3, vol/vol) was layered on top of 10 l of urea (6 M) in Eppendorf tubes; 50 l of [ 3 H]fMLF (8 ϫ 10 Ϫ8 M) together with 50 l of KRG or unlabeled fMLF (4 ϫ 10 Ϫ5 M) in KRG was layered on top of the oil.…”

Section: Methodsmentioning

confidence: 99%

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Lipopolysaccharide-Induced Gelatinase Granule Mobilization Primes Neutrophils for Activation by Galectin-3 and Formylmethionyl-Leu-Phe

et al. 2001

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We have earlier shown that galectin-3, a lactose-binding mammalian lectin that is secreted from activated macrophages, basophils, and mast cells, induces activation of the NADPH oxidase in exudated but not in peripheral blood neutrophils (A. Karlsson, P. Follin, H. Leffler, and C. Dahlgren, Blood 91:3430-3438, 1998). The alteration in responsiveness occurring during extravasation correlated with mobilization of the gelatinase and/or specific granules to the cell surface, indicating a role for mobilizable galectin-3 receptors. In this study we have investigated galectin-3-induced NADPH oxidase activation, measured as superoxide production, in lipopolysaccharide (LPS)-primed neutrophils. Upon galectin-3 challenge, the LPS-primed cells produced superoxide, both extracellularly and intracellularly. A primed extracellular response to formylmethionyl-LeuPhe (fMLF) was also achieved. The exposure of complement receptors 1 and 3 as well as the formyl peptide receptor on the cell surface was markedly increased after LPS treatment, indicating that granule fusion with the plasma membrane had occurred. Further assessment of specific markers for neutrophil granules showed that the LPS treatment had mobilized the gelatinase granules but only a minor fraction of the specific granules. We thus suggest that the mechanism behind LPS priming lies at the level of granule (receptor) mobilization for galectin-3 as well as for fMLF.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Lipopolysaccharide-Induced Gelatinase Granule Mobilization Primes Neutrophils for Activation by Galectin-3 and Formylmethionyl-Leu-Phe

et al. 2001

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“…7B, neutrophils were primed in their response to Cmp1 by the cytokine TNF-␣, the primed neutrophils produced at least 5 times (measured as peak values) more superoxide anions than did naive neutrophils, and the production reached levels comparable to that induced by fMLF. Previous studies have shown that many neutrophil receptors, including FPR1 and FPR2, are stored in secretory organelles of naive cells (34)(35)(36), and mobilization of FPRs to the cell surface is accompanied with a primed FPR response, suggesting a possible role for granule mobilization in mediating priming.…”

Section: Cmp1 Activates the Phospholipase C-inositol Phosphate 3 (Ip mentioning

confidence: 98%

The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment

Björkman

Mårtensson

Winther

et al. 2016

Molecular and Cellular Biology

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c Ligands with improved potency and selectivity for free fatty acid receptor 2 (FFA2R) have become available, and we here characterize the neutrophil responses induced by one such agonist (Cmp1) and one antagonist (CATPB). Cmp1 triggered an increase in the cytosolic concentration of Ca 2؉ , and the neutrophils were then desensitized to Cmp1 and to acetate, a naturally occurring FFA2R agonist. The antagonist CATPB selectively inhibited responses induced by Cmp1 or acetate. The activated FFA2R induced superoxide anion secretion at a low level in naive blood neutrophils. This response was largely increased by tumor necrosis factor alpha (TNF-␣) in a process associated with a recruitment of easily mobilizable granules, but neutrophils recruited to an aseptic inflammation in vivo were nonresponding. Superoxide production induced by Cmp1 was increased in latrunculin Atreated neutrophils, but no reactivation of desensitized FFA2R was induced by this drug, suggesting that the cytoskeleton is not directly involved in terminating the response. The functional and regulatory differences between the receptors that recognize short-chain fatty acids and formylated peptides, respectively, imply different roles of these receptors in the orchestration of inflammation and confirm the usefulness of a selective FFA2R agonist and antagonist as tools for the exploration of the precise role of the FFA2R.

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“…For experiments determining the ability of AAT to act as an inhibitor of LTB 4 BLT1 signaling, healthy control neutrophils (2 3 10 6 cells/ml) were first challenged with PMA (100 ng) for 10 min at 37˚C to increase membrane levels of the BLT1 receptor (60). Cells were then untreated or were treated with LTB 4 (100 nM) in the presence or absence of AAT (27.5 mM) or U-75302 (1 mM) for 10 min or 100 nM NE for 0, 15, or 30 min at 37˚C.…”

Section: Flow Cytometric Assaysmentioning

confidence: 99%

The BLT1 Inhibitory Function of α-1 Antitrypsin Augmentation Therapy Disrupts Leukotriene B4 Neutrophil Signaling

O’Dwyer

O’Brien

Wormald

et al. 2015

The Journal of Immunology

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Leukotriene B4 (LTB4) contributes to many inflammatory diseases, including genetic and nongenetic forms of chronic obstructive pulmonary disease. α-1 Antitrypsin (AAT) deficiency (AATD) is characterized by destruction of lung parenchyma and development of emphysema, caused by low AAT levels and a high neutrophil burden in the airways of affected individuals. In this study we assessed whether AATD is an LTB4-related disease and investigated the ability of serum AAT to control LTB4 signaling in neutrophils. In vitro studies demonstrate that neutrophil elastase is a key player in the LTB4 inflammatory cycle in AATD, causing increased LTB4 production, and associated BLT1 membrane receptor expression. AATD patients homozygous for the Z allele were characterized by increased neutrophil adhesion and degranulation responses to LTB4. We demonstrate that AAT can bind LTB4 and that AAT/LTB4 complex formation modulates BLT1 engagement and downstream signaling events, including 1,4,5-triphosphate production and Ca2+ flux. Additionally, treatment of ZZ-AATD individuals with AAT augmentation therapy decreased plasma LTB4 concentrations and reduced levels of membrane-bound neutrophil elastase. Collectively, these results provide a mechanism by which AAT augmentation therapy impacts on LTB4 signaling in vivo, and not only reinforces the utility of this therapy for resolving inflammation in AATD, but supports useful future clinical applications in treatment of other LTB4-related diseases.

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Cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Correlation to changes in the cytosolic free Ca2+ level and action of phorbol myristate acetate.

Abstract: We have studied how cytosolic free Ca2" ([Ca2+Ii)

Cited by 65 publications

References 43 publications

Lipopolysaccharide-Induced Gelatinase Granule Mobilization Primes Neutrophils for Activation by Galectin-3 and Formylmethionyl-Leu-Phe

Lipopolysaccharide-Induced Gelatinase Granule Mobilization Primes Neutrophils for Activation by Galectin-3 and Formylmethionyl-Leu-Phe

The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment

The BLT1 Inhibitory Function of α-1 Antitrypsin Augmentation Therapy Disrupts Leukotriene B4 Neutrophil Signaling

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