A step sensitive to pertussis toxin and phorbol ester in human neutrophils regulates chemotaxis and capping but not phagocytosis

Lad, Pramod M.; Olson, Charles V.; Grewal, Iqbal S.

doi:10.1016/0014-5793(86)80517-8

Cited by 28 publications

(6 citation statements)

References 29 publications

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“…Even at a sixfold higher toxin concentration, phagocytosis and the associated generation of second messengers were largely unaffected. This agrees well with a previous study (although that study dealt with a different kind of particle and much higher concentrations ofpertussis toxin), which failed to demonstrate that pertussis toxin had any effect at all on receptor-mediated phagocytosis (26). In contrast, both chemotactic and secretory functions elicited by chemoattractants such as FMLP, C5a, and LTB4 are entirely suppressed by pertussis toxin.…”

Section: Discussionsupporting

confidence: 92%

Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol. Elevation in cytosolic free calcium and formation of inositol phosphates can be dissociated from accumulation of diacylglycerol.

Fällman¹,

Lew²,

Stendahl³

et al. 1989

J. Clin. Invest.

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Phagocytosis of C3bi-or IgG-opsonized yeast particles in human neutrophils was found to be associated with an increased formation of inositol phosphates and diacylglycerol. Pertussis toxin only marginally affected phagocytosis of IgGand C3bi-opsonized particles and the associated formation of second messengers. Forskolin, which induced a threefold rise of cellular cAMP, however, markedly inhibited both C3bi-and IgG-mediated phagocytosis as well as the particle-induced formation of inositol phosphates and diacylglycerol. These observations are in contrast to what was found to occur with chemotactic factors and indicate that chemotactic and phagocytic signaling can be regulated independently in human neutrophils.Since C3bi-mediated phagocytosis has been shown to occur at vanishingly low cytosolic free calcium levels, calcium-depleted cells were used to study the importance of the inositol cycle for the engulfment of C3bi-opsonized particles. Despite a total lack of receptor-induced formation of inositol phosphates, a significantly increased accumulation of diacylglycerol accompanied the ingestion of C3bi-opsonized particles. These data show that the engulfment of C3bi-opsonized particles can occur independently of both a calcium transient and an increased inositol phosphate production. However, the observed accumulation of diacylglycerol, not derived from phosphoinositides, suggests that this second messenger play a role in the control of the engulfment process.

show abstract

Section: Discussionsupporting

confidence: 92%

Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol. Elevation in cytosolic free calcium and formation of inositol phosphates can be dissociated from accumulation of diacylglycerol.

Fällman¹,

Lew²,

Stendahl³

et al. 1989

J. Clin. Invest.

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“…Pertussis toxin provided the first indications of a critical mediatory role for a G protein in neutrophil activation by soluble agonists (45). On the other hand, pertussis toxin has been reported to inhibit stimulated monocyte phagocytosis (46) but not unstimulated neutrophil phagocytosis (47). GM-CSF is known to modulate the functional responsiveness of neutrophils to soluble stimuli such as peptidic and lipidic chemotactic factors (48,49).…”

Section: Discussionmentioning

confidence: 99%

Crystal‐induced neutrophil activation. I. Initiation and modulation of calcium mobilization and superoxide production by microcrystals

Naccache

Grimard

Roberge

et al. 1991

Arthritis & Rheumatism

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The effects of monosodium urate and calcium pyrophosphate dihydrate crystals on the levels of cytoplasmic free calcium and on the oxidative burst in normal human blood neutrophils were examined. The pattern of sensitivity to granulocyte-macrophage colony-stimulating factor, colchicine, cytochalasin B, pertussis toxin, diglyceride kinase, and protein kinase C inhibitors differentiated the mechanism(s) of neutrophil activation by the crystals from that involved in the responses to soluble chemotactic factors and indicated that individual crystals can use several activation pathways.

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“…The signal transduction cascade initiated by these receptors has also been shown to be essential since treatment of cells with pertussis toxin, which blocks the interaction of G i proteins with receptors, completely abolishes leukocyte chemotaxis (23)(24)(25). Furthermore, actin polymerization has been demonstrated to be essential, since cytochalasins, which block actin polymerization, also abolish chemotaxis (26,27).…”

Section: Resultsmentioning

confidence: 99%

Phosphorylation of the N-Formyl Peptide Receptor Is Required for Receptor Internalization but Not Chemotaxis

Hsu

Chiang

et al. 1997

Journal of Biological Chemistry

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The human N-formyl peptide receptor (FPR) is a member of the family of leukocyte, G protein-coupled, chemoattractant receptors. To determine the role(s) of receptor phosphorylation in FPR processing and formylmethionylleucylphenylalanine (fMLF)-mediated chemotaxis, we utilized U937 cells expressing the recombinant wild type receptor and a mutant form of the FPR. This mutant, which lacks all of the serine and threonine residues in the C terminus of the receptor, ⌬ST, has recently been shown to produce a receptor capable of fMLF binding and G protein activation but was demonstrated not to undergo fMLF-dependent phosphorylation or desensitization of the calcium mobilization response upon repeated exposure to agonist (Prossnitz, E. R. (1997) J. Biol. Chem. 272, 15213-15219). In this report, we examined the role of receptor phosphorylation in FPR internalization and leukocyte chemotaxis. Whereas the wild type receptor was rapidly internalized upon stimulation, the phosphorylation-deficient mutant was not, remaining entirely on the cell surface. In addition, contrary to the hypothesis that receptor processing and recycling are required for chemotaxis, we found no defect in the ability of the mutant FPR to migrate up a concentration gradient of fMLF. These results indicate that phosphorylation of the FPR is a necessary step in receptor internalization but that receptor phosphorylation, desensitization, and internalization are not required for chemotaxis.Neutrophils normally exist in a resting state as they circulate though the body. However, upon interaction with small molecules known as chemoattractants, they rapidly respond with endothelial adhesion followed by emigration from the vasculature and chemotaxis to the site of inflammation (1). Chemoattractants activate neutrophils through binding to heptahelical receptors located on the cell surface (2, 3). These receptors activate heterotrimeric GTP-binding proteins (G proteins) 1 that initiate numerous elaborate signal transduction cascades, culminating in neutrophil migration and activation. Once at the site of inflammation, neutrophils respond with phagocytosis, superoxide generation, and the release of degradative enzymes (4). One of the most thoroughly studied chemoattractant receptors is the N-formyl peptide receptor (FPR), which recognizes short N-formylated oligopeptides of bacterial or mitochondrial origin (5-7).Leukocyte chemotaxis has been shown to be dependent on the binding of chemoattractants to their respective receptors (8,9). Following binding of the ligand and cellular activation, the receptors undergo desensitization and internalization (10, 11). Once internalized, ligand dissociates from the receptor and is degraded, whereupon the receptor is recycled to the cell surface for additional rounds of activation (10). Receptor recycling has been suggested to be essential for sustained cellular responses, such as cell chemotaxis (12, 13). Inhibition of receptor recycling through exposure to wheat germ agglutinin or by neuraminidase treatment was found to ...

show abstract

A step sensitive to pertussis toxin and phorbol ester in human neutrophils regulates chemotaxis and capping but not phagocytosis

Cited by 28 publications

References 29 publications

Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol. Elevation in cytosolic free calcium and formation of inositol phosphates can be dissociated from accumulation of diacylglycerol.

Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol. Elevation in cytosolic free calcium and formation of inositol phosphates can be dissociated from accumulation of diacylglycerol.

Crystal‐induced neutrophil activation. I. Initiation and modulation of calcium mobilization and superoxide production by microcrystals

Phosphorylation of the N-Formyl Peptide Receptor Is Required for Receptor Internalization but Not Chemotaxis

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