The increase in intracellular free calcium associated with IgG gamma 2b/gamma 1 Fc receptor-ligand interactions: role in phagocytosis.

Young, John Ding‐E; Ko, Sandy S.; Cohn, Zanvil A.

doi:10.1073/pnas.81.17.5430

Cited by 132 publications

(81 citation statements)

References 14 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lipoxygenase pathways in macrophages are not constitutive, but are presumably activated by the Ca2l fluxes accompanying membrane perturbation (23,24). Generation of compound X and the monoHETEs correlated directly with the extent of phagocytosis of viable T. gondii.…”

Section: Discussionmentioning

confidence: 99%

Alteration of leukotriene release by macrophages ingesting Toxoplasma gondii.

Locksley¹,

Fankhauser²,

Henderson³

1985

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Mouse resident peritoneal macrophages incubated with ionophore A23187 or opsonized zymosan released leukotrienes (LT) B4 and C4 (LTB4 and LTC4) and LTC4 and LTD4, respectively. In contrast, incubation with Toxoplasma gondii, an obligate intracellular protozoan, led to the formation of 11-, 12-, and 15-hydroxyicosatetraenoic acids (HETEs), together with an unidentified compound, designated compound X. Each of these compounds incorporated [3H]arachidonic acid from the macrophage during phagocytosis of T. gondi. Compound X migrated immediately prior to 15-HETE by reversephase HPLC and was distinct from authentic monoHETE, monohydroperoxyicosatetraenoic acid (mono-HPETE), and dihydroxyicosatetraenoic acid (diHETE) standards. The generation of compound X by macrophages correlated with the extent of phagocytosis of T. gondii and with intracellular survival of the organisms. Prior antibody-coating of T. gondii or activation of macrophages, either of which inhibited survival and replication of ingested organisms, was associated with production of LTD4 but not compound X. Killed organisms also stimulated LTD4 release only. Although T. gondii concentrated arachidonic acid, they did not metabolize the compound to identifiable lipoxygenase products. Preincubation of macrophages with the relative lipoxygenase inhibitors nordihydroguaiaretic acid or 5,8,11,14-icosatetraynoic acid inhibited the formation of compound X. The absence of leukotriene production by macrophages ingesting T. gondji may explain the relative lack of a neutrophil inflammatory response in diseases due to obligate intracellular organisms. Alternatively, compound X may have functional activities that might mediate some of the host responses to cellular parasitism.The leukotrienes (LT) have been identified as potentially important inflammatory mediators of host defense (1, 2). LTB4 is a potent neutrophil chemoattractant and stimulus for aggregation, degranulation, and adherence to endothelium. The sulfidopeptide leukotrienes LTC4, LTD4, and LTE4, which collectively constitute the slow-reacting substance of anaphylaxis (SRS), promote vasoconstriction and enhance permeability across the postcapillary venule. Resident tissue macrophages are major sources of the LT (3-5). The plasma membrane of these cells is rich in esterified arachidonate that is released during membrane perturbation and is then available to Ca2+-dependent 5-lipoxygenase that regulates the formation of the LT (6, 7). Traditional stimuli for LT production by macrophages in vitro include both soluble (calcium ionophore A23187, endotoxin, phorbol myristate acetate) and particulate (zymosan, immunocomplexes) stimuli; LT production in response to the latter has been related directly to the degree of phagocytosis (3-5).Resident tissue macrophages are the initial target of many obligate intracellular pathogens that infect man, but the capacity of viable organisms to trigger the release of inflammatory mediators from macrophages has not been systematically investigated. The pathogenic protozoa...

show abstract

Section: Discussionmentioning

confidence: 99%

Alteration of leukotriene release by macrophages ingesting Toxoplasma gondii.

Locksley¹,

Fankhauser²,

Henderson³

1985

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Macrophage β-AR stimulation also inhibits activation of Ca 2+ -dependent K + channels [177], while stimulation of α 1 -AR on macrophages activates Ca 2+ -dependent K + channels by mobilizing intracellular Ca 2+ stores, presumably via the activation of phospholipase C and a G-protein-dependent mechanism [188]. Activation of Ca 2+ -dependent K + channels is important for modulating macrophage phagocytic activity and may explain the α-AR-mediated enhancement of macrophage phagocytic activity [189]. The functional effects of stimulation of AR on macrophages are dependent on the subtype of receptor.…”

Section: Macrophagesmentioning

confidence: 99%

Sympathetic modulation of immunity: Relevance to disease

Bellinger

Millar

Perez

et al. 2008

Cellular Immunology

223

185

View full text Add to dashboard Cite

Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far as focused on neural-immune modulation in secondary lymphoid organs, and have revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS-immune interaction may enhance immune readiness during disease-or injury-induced 'fight' responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks.

show abstract

“…The transduction mechanisms regulating the phagocytic process have so far only been partly elucidated. What is known is that receptor-mediated phagocytosis occurring via the two major opsonins is associated with a rise in the concentration of cytosolic free Ca2l (2)(3)(4). Even more interesting are the observations that in human neutrophils only IgG-mediated ingestion is actually dependent on the rise of cytosolic cells) the rise in intracellular Ca2" is not a requirement for the phagocytic uptake of IgG-opsonized particles (2).…”

Section: Introductionmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

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

The increase in intracellular free calcium associated with IgG gamma 2b/gamma 1 Fc receptor-ligand interactions: role in phagocytosis.

Cited by 132 publications

References 14 publications

Alteration of leukotriene release by macrophages ingesting Toxoplasma gondii.

Alteration of leukotriene release by macrophages ingesting Toxoplasma gondii.

Sympathetic modulation of immunity: Relevance to disease

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.

Contact Info

Product

Resources

About