Effect of Cyclic AMP Level Reduction on Human Neutrophil Responses to Formylated Peptides

Spisani, Susanna; Pareschi, Maria Cristina; Buzzi, Marco; Colamussi, Maria Luisa; Biondi, Carla; Traniello, Serena; Zecchini, Giampiero Pagani; Paradisi, Mario Paglialunga; Torrini, I.; Ferretti, Maria Enrica

doi:10.1016/0898-6568(96)00049-6

Cited by 46 publications

(39 citation statements)

References 33 publications

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“…Whereas chemoattractants, particularly fMLP, have previously been shown to increase total cAMP levels in neutrophils, the mechanism by which this occurs has remained unclear (Simchowitz et al, 1980;Smolen et al, 1980;Spisani et al, 1996;Suzuki et al, 1996;Ali et al, 1998). Cyclic AMP production is regulated by its synthesis through the activation of ACs and its degradation by phosphodiesterases.…”

Section: Discussionmentioning

confidence: 99%

“…Chemoattractants bind to serpentine transmembrane receptors that couple to heterotrimeric G proteins (Murphy, 1996). Receptor activation leads to the dissociation of the G protein into ␣-and ␤␥-subunits, which go on to stimulate a variety of effectors that ultimately lead to cellular polarization and migration.Several studies have established that the addition of chemoattractants to neutrophils causes an increase in the production of cAMP (Simchowitz et al, 1980;Smolen et al, 1980;Spisani et al, 1996;Suzuki et al, 1996;Ali et al, 1998). Although a clear correlation between total cAMP levels and chemotaxis has not been established, many studies have shown that, in neutrophils, increases in cAMP levels inhibit chemotaxis (Harvath et al, 1991;Elferink and VanUffelen, 1996;VanUffelen et al, 1998;Ariga et al, 2004).…”

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A Chemoattractant-mediated G_i-coupled Pathway Activates Adenylyl Cyclase in Human Neutrophils

Mahadeo

Janka-Junttila

Smoot

et al. 2007

MBoC

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Neutrophils and Dictyostelium use conserved signal transduction pathways to decipher chemoattractant gradients and migrate directionally. In both cell types, addition of chemoattractants stimulates the production of cAMP, which has been suggested to regulate chemotaxis. We set out to define the mechanism by which chemoattractants increase cAMP levels in human neutrophils. We show that chemoattractants elicit a rapid and transient activation of adenylyl cyclase (AC). This activation is sensitive to pertussis toxin treatment but independent of phosphoinositide-3 kinase activity and an intact cytoskeleton. Remarkably, and in sharp contrast to G␣ s -mediated activation, chemoattractant-induced AC activation is lost in cell lysates. Of the nine, differentially regulated transmembrane AC isoforms in the human genome, we find that isoforms III, IV, VII, and IX are expressed in human neutrophils. We conclude that the signal transduction cascade used by chemoattractants to activate AC is conserved in Dictyostelium and human neutrophils and is markedly different from the canonical G␣ s -meditated pathway. INTRODUCTIONMany types of cells have the ability to migrate directionally when exposed to gradients of chemoattractants. This chemotactic response is essential for a variety of physiological processes and is initiated when chemoattractants bind surface receptors and activate a wide range of signal transduction cascades, which ultimately lead to cellular polarization and migration (Parent, 2004). The acquisition of polarity is accompanied by a dramatic redistribution of cytoskeletal components, where F-actin and numerous actin-binding proteins are enriched at the front or leading edge and myosin II is assembled on the sides and at the back or trailing edge (Van Haastert and Devreotes, 2004;Bagorda et al., 2006).A striking chemotactic behavior is exhibited by neutrophils as they move across vascular barriers and navigate to sites of inflammation (Niggli, 2003b;Parent, 2004). The agents that induce directed migration of neutrophils include a large and diverse group of chemoattractants originating from different sources (Uhing and Snyderman, 1999). These agents include formylated peptides secreted by bacteria (such as N-formylmethionyl-leucyl-phenylalanine [fMLP]), products of the complement cascade (such as complement factor 5a [C5a]), and phospholipid metabolites (such as leukotriene B4 [LTB 4 ]) as well as a large family of chemokines that are derived from endothelial, epithelial, and stromal cells (Baggiolini, 1998). Remarkably, neutrophils can also relay the signal to surrounding cells by stimulating the production and release of more attractants, such as LTB 4 and interleukin (IL)-8, which act in a paracrine manner to spread the chemotactic response to surrounding cells (Bazzoni et al., 1991;Baggiolini et al., 1994;Kannan, 2002). Chemoattractants bind to serpentine transmembrane receptors that couple to heterotrimeric G proteins (Murphy, 1996). Receptor activation leads to the dissociation of the G protein into ␣-and...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A Chemoattractant-mediated G_i-coupled Pathway Activates Adenylyl Cyclase in Human Neutrophils

Mahadeo

Janka-Junttila

Smoot

et al. 2007

MBoC

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“…It is not clear, however, if all of the inhibitory activities of adenosine on PMN functions depend on an elevation of intracellular cAMP levels (Spisani et al, 1996), and some studies have shown that the inhibition of superoxide anion synthesis was not blocked by a protein kinase A inhibitor (Cronstein et al, 1992), underlining the probable involvement of other kinases or signaling pathways. Moreover, intracellular signaling events that mediate the actions of adenosine are often cell-specific, and are certainly not thoroughly characterized in leukocytes.…”

Section: Introductionmentioning

confidence: 99%

Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal

Cadieux

Leclerc

St-Onge

et al. 2005

Journal of Cell Science

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Neutrophils, which are often the first to migrate at inflamed sites, can generate leukotriene B4 from the 5-lipoxygenase pathway and prostaglandin E2 through the inducible cyclooxygenase-2 pathway. Adenosine, an endogenous autacoid with several anti-inflammatory properties, blocks the synthesis of leukotriene B4 while it potentiates the cyclooxygenase-2 pathway in fMLP-treated neutrophils, following activation of the A2A receptor. Using the murine air pouch model of inflammation, we observed that inflammatory leukocytes from mice lacking the A2A receptor have less cyclooxygenase-2 induction than wild-type animals. In human leukocytes, A2A receptor activation specifically elicited potentiation of cyclooxygenase-2 in neutrophils, but not in monocytes. Signal transduction studies indicated that the cAMP, ERK1/2, PI-3K and p38K intracellular pathways are implicated both in the direct upregulation of cyclooxygenase-2 and in its potentiation. Together, these results indicate that neutrophils are particularly important mediators of adenosine's effects. Given the uncontrolled inflammatory phenotype observed in knockout mice and in view of the potent inhibitory actions of prostaglandin E2 on inflammatory cells, an increased cyclooxygenase-2 expression resulting from A2A receptor activation, observed particularly in neutrophils, may take part in an early modulatory mechanism promoting anti-inflammatory activities of adenosine.

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“…O 2 ⅐ release was monitored continuously with a temperature-controlled spectrophotometer by the reduction of ferricytochrome c inhibited by superoxide dismutase, as described previously (Spisani et al, 1992). The mixture was incubated with either control or different concentrations of agonists for 5 min at 37°C.…”

Section: Materials [mentioning

confidence: 99%

A₃Adenosine Receptors in Human Neutrophils and Promyelocytic HL60 Cells: A Pharmacological and Biochemical Study

et al. 2002

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This work compares the pharmacological and biochemical properties of A 3 adenosine receptors in human polymorphonuclear neutrophil granulocytes (PMNs) and promyelocytic HL60 cells. The gene expression of A 3 receptors was examined by reverse transcription-polymerase chain reaction experiments, whereas the amount of A 3 subtype on the plasma membrane was quantified by using the high-affinity and selective A 3 antagonist -(3-iodo-benzyl)-2-chloro-adenosine-5Ј-N-methyluronamide (Cl-IB-MECA) for inhibition of cAMP levels via A 3 receptors are in good agreement with the binding data; furthermore, the response is potently inhibited by MRE 3008F20. In contrast, the high micromolar concentrations of Cl-IB-MECA and MRE 3008F20 in stimulating and blocking Ca 2ϩ mobilization, respectively, are not completely consistent with the involvement of an A 3 receptor. Furthermore, an important finding of this work is that the inhibition of PMNs oxidative burst is predominantly A 2A -mediated, even though an effect of A 3 subtype could not be excluded. This conclusion is based on potent blockade of Cl-IB-MECA-mediated inhibition of oxidative burst by SCH 58261 and a minor but significant blockade by MRE 3008F20. In conclusion, HL60 cells express A 3 receptors similar to those in PMNs, thus providing a useful model for investigation of biochemical pathways leading to A 3 receptor activation.Neutrophils play major roles in host defense against the invasion of microorganisms and in acute inflammation and have been implicated in the pathogenesis of a number of human diseases. Adenosine, which has been identified as an important regulator of neutrophil function, particularly with regard to neutrophil superoxide production and neutrophil adherence, may therefore be protective against neutrophilmediated tissue injury (Firestein et al., 1995;Cronstein, 1997). So far, four adenosine receptors have been classified (A 1 , A 2A , A 2B , and A 3 ), all of which are coupled to G proteins (Fredholm et al., 2000;Linden, 2001). Human neutrophils contain both A 2A and A 1 subtypes, which produce opposite effects on several cell functions (Fredholm et al., 1996): activation of A 1 by adenosine at low concentrations is associated with augmentation of chemotaxis and phagocytosis (Sullivan and Linden, 1998), whereas occupation of A 2A by adenosine

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Effect of Cyclic AMP Level Reduction on Human Neutrophil Responses to Formylated Peptides

Cited by 46 publications

References 33 publications

A Chemoattractant-mediated G_i-coupled Pathway Activates Adenylyl Cyclase in Human Neutrophils

A Chemoattractant-mediated G_i-coupled Pathway Activates Adenylyl Cyclase in Human Neutrophils

Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal

A₃Adenosine Receptors in Human Neutrophils and Promyelocytic HL60 Cells: A Pharmacological and Biochemical Study

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Effect of Cyclic AMP Level Reduction on Human Neutrophil Responses to Formylated Peptides

Cited by 46 publications

References 33 publications

A Chemoattractant-mediated Gi-coupled Pathway Activates Adenylyl Cyclase in Human Neutrophils

A Chemoattractant-mediated Gi-coupled Pathway Activates Adenylyl Cyclase in Human Neutrophils

Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal

A3Adenosine Receptors in Human Neutrophils and Promyelocytic HL60 Cells: A Pharmacological and Biochemical Study

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A Chemoattractant-mediated G_i-coupled Pathway Activates Adenylyl Cyclase in Human Neutrophils

A Chemoattractant-mediated G_i-coupled Pathway Activates Adenylyl Cyclase in Human Neutrophils

A₃Adenosine Receptors in Human Neutrophils and Promyelocytic HL60 Cells: A Pharmacological and Biochemical Study