scholarly journals Development, characterisation and in vitro evaluation of lanthanide-based FPR2/ALX-targeted imaging probes

2019 ◽  
Vol 48 (44) ◽  
pp. 16764-16775 ◽  
Author(s):  
Tamara Boltersdorf ◽  
Junaid Ansari ◽  
Elena Y. Senchenkova ◽  
Lijun Jiang ◽  
Andrew J. P. White ◽  
...  
Keyword(s):  
Lanthanide Complexes ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Targeted Imaging ◽  
In Vitro Evaluation ◽  
Peptide Receptor ◽  
Imaging Probes ◽  
Formyl Peptide

Formyl Peptide Receptor (FPR)-targeted lanthanide complexes with long-lived emission in stimulated human neutrophils.

scholarly journals Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils.

1993 ◽  
Vol 123 (4) ◽  
pp. 895-907 ◽  
Author(s):  
B A McCormick ◽  
S P Colgan ◽  
C Delp-Archer ◽  
S I Miller ◽  
J L Madara
Keyword(s):  
Epithelial Cells ◽  
Salmonella Typhimurium ◽  
Apical Membrane ◽  
Coli Strain ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Classical Pathway ◽  
Intestinal Epithelial ◽  
Formyl Peptide

In human intestinal disease induced by Salmonella typhimurium, transepithelial migration of neutrophils (PMN) rapidly follows attachment of the bacteria to the epithelial apical membrane. In this report, we model those interactions in vitro, using polarized monolayers of the human intestinal epithelial cell, T84, isolated human PMN, and S. typhimurium. We show that Salmonella attachment to T84 cell apical membranes did not alter monolayer integrity as assessed by transepithelial resistance and measurements of ion transport. However, when human neutrophils were subsequently placed on the basolateral surface of monolayers apically colonized by Salmonella, physiologically directed transepithelial PMN migration ensued. In contrast, attachment of a non-pathogenic Escherichia coli strain to the apical membrane of epithelial cells at comparable densities failed to stimulate a directed PMN transepithelial migration. Use of the n-formyl-peptide receptor antagonist N-t-BOC-1-methionyl-1-leucyl-1- phenylalanine (tBOC-MLP) indicated that the Salmonella-induced PMN transepithelial migration response was not attributable to the classical pathway by which bacteria induce directed migration of PMN. Moreover, the PMN transmigration response required Salmonella adhesion to the epithelial apical membrane and subsequent reciprocal protein synthesis in both bacteria and epithelial cells. Among the events stimulated by this interaction was the epithelial synthesis and polarized release of the potent PMN chemotactic peptide interleukin-8 (IL-8). However, IL-8 neutralization, transfer, and induction experiments indicated that this cytokine was not responsible for the elicited PMN transmigration. These data indicate that a novel transcellular pathway exists in which subepithelial PMN respond to lumenal pathogens across a functionally intact epithelium. Based on the known unique characteristics of the intestinal mucosa, we speculate that IL-8 may act in concert with an as yet unidentified transcellular chemotactic factor(s) (TCF) which directs PMN migration across the intestinal epithelium.

Cloning of a cDNA encoding a receptor related to the formyl peptide receptor of human neutrophils

Gene ◽  
1992 ◽  
Vol 118 (2) ◽  
pp. 303-304 ◽  
Author(s):  
H.Daniel Perez ◽  
Richard Holmes ◽  
Edward Kelly ◽  
John McClary ◽  
William H. Andrews
Keyword(s):  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Peptide Receptor ◽  
Formyl Peptide

scholarly journals N-Formyl peptide receptor subtypes in human neutrophils activate l-plastin phosphorylation through different signal transduction intermediates

2004 ◽  
Vol 377 (2) ◽  
pp. 469-477 ◽  
Author(s):  
Marie-Hélène PACLET ◽  
Clare DAVIS ◽  
Peter KOTSONIS ◽  
Jasminka GODOVAC-ZIMMERMANN ◽  
Anthony W. SEGAL ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Formyl Peptide Receptor ◽  
Actin Binding ◽  
Human Neutrophils ◽  
Receptor Subtypes ◽  
Peptide Receptor ◽  
High Affinity ◽  
Formyl Peptide ◽  
Fmlp Receptor ◽  
Phosphoinositide 3 Kinase

We investigated the coupling of the fMLP (N-formyl-l-methionyl-l-leucyl-l-phenylalanine; ‘chemotactic peptide’) receptor with phosphorylation of the actin-binding protein l-plastin in neutrophils. Using two-dimensional IEF (isoelectric focusing)/PAGE and MALDI–TOF (matrix-assisted laser desorption ionization–time-of-flight)-MS, l-plastin was identified as a major phosphoprotein in fMLP-stimulated neutrophils whose phosphorylation was dependent on phosphoinositide 3-kinase, PLD (phospholipase D) and PKC (protein kinase C) activity. Two fMLP receptor subtypes were identified in neutrophils, characterized by a distinct sensitivity to fMLP and antagonistic peptides. Both receptor subtypes induced the phosphorylation of l-plastin. l-plastin phosphorylation induced by low-affinity fMLP receptors involves an action of phosphoinositide 3-kinase, PLD and PKC isotypes. In contrast, none of these intermediates are utilized by high-affinity fMLP receptors in the phosphorylation of l-plastin. However, the PKC inhibitor Ro-31-8220 inhibits l-plastin phosphorylation induced by the high-affinity fMLP receptor. Thus, an as yet unknown Ro-31-8220-sensitive kinase regulates l-plastin phosphorylation in response to the high-affinity fMLP receptor. The results suggest a model in which receptor subtypes induce a similar endpoint event through different signal-transduction intermediates. This may be relevant in the context of cell migration in which one receptor subpopulation may become desensitized in a concentration gradient of chemoattractant.

Human neutrophils are activated by a peptide fragment ofClostridium difficiletoxin B presumably via formyl peptide receptor

2015 ◽  
Vol 17 (6) ◽  
pp. 893-909 ◽  
Author(s):  
Sebastian D. Goy ◽  
Alexandra Olling ◽  
Detlef Neumann ◽  
Andreas Pich ◽  
Ralf Gerhard
Keyword(s):  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Peptide Fragment ◽  
Peptide Receptor ◽  
Formyl Peptide

scholarly journals N-formyl peptide receptors in human neutrophils display distinct membrane distribution and lateral mobility when labeled with agonist and antagonist.

1993 ◽  
Vol 121 (6) ◽  
pp. 1281-1289 ◽  
Author(s):  
B Johansson ◽  
M P Wymann ◽  
K Holmgren-Peterson ◽  
K E Magnusson
Keyword(s):  
Confocal Microscopy ◽  
Lateral Diffusion ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Lateral Mobility ◽  
Peptide Receptors ◽  
Tetrazolium Chloride ◽  
Formyl Peptide Receptors ◽  
Peptide Receptor ◽  
Formyl Peptide

Receptors for bacterial N-formyl peptides are instrumental for neutrophil chemotactic locomotion and activation at sites of infection. As regulatory mechanisms for signal transduction, both rapid coupling of the occupied receptor to cytoskeletal components, and receptor lateral redistribution, have been suggested (Jesaitis et al., 1986, 1989). To compare the distribution and lateral diffusion of the nonactivated and activated neutrophil N-formyl-peptide receptor, before internalization, we used a new fluorescent N-formyl-peptide receptor antagonist, tertbutyloxycarbonyl-Phe(D)-Leu-Phe(D)-Leu-Phe-OH (Boc-FLFLF, 0.1-1 microM), and the fluorescent receptor agonist formyl-Nle-Leu-Phe-Nle-Tyr-Lys (fnLLFnLYK, 0.1-1 microM). Fluorescent Boc-FLFLF did not elicit an oxidative burst in the neutrophil at 37 degrees C, as assessed by chemiluminescence and reduction of p-nitroblue tetrazolium chloride, but competed efficiently both with formyl-methionyl-leucyl-phenylalanine (fMLF) and fnLLFnLYK. It was not internalized, as evidenced by confocal microscopy and acid elution of surface bound ligand. The lateral mobility characteristics of the neutrophil fMLF receptor were investigated with the technique of FRAP. The diffusion coefficient (D) was similar for antagonist- and agonist-labeled receptors (D approximately 5 x 10(-10) cm2/s), but the fraction of mobile receptors was significantly lower in agonist- compared to antagonist-labeled cells, approximately 40% in contrast to approximately 60%. This reduction in receptor mobile fraction was slightly counteracted, albeit not significantly, by dihydrocytochalasin B (dhcB, 5 microM). To block internalization of agonist-labeled receptors, receptor mobility measurements were done at 14 degrees C. At this temperature, confocal microscopy revealed clustering of receptors in response to agonist binding, compared to a more uniform receptor distribution in antagonist-labeled cells. The pattern of agonist-induced receptor clustering was less apparent after dhcB treatment. To summarize, this work shows that activated N-formyl peptide receptors aggregate and immobilize in the plane of the neutrophil plasma membrane before internalization, a process that is affected, but not significantly reversed, by cytochalasin. The results are consistent with a model where arrested receptors are associated mainly with a cytochalasin-insensitive pool of cytoskeletal elements.

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