Mechanisms of Mediator Release from Inflammatory Cells

Henson, Peter M.

doi:10.1007/978-1-4684-0745-7_2

Cited by 38 publications

(33 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings have been confirmed and extended in human neutrophils by our group (6,18,19). In these studies (18,19), we observed that, after exposure of human neutrophils to 100 nM FMLP in 140 mM Na medium, pHo 7 (1) It thus appears that the chemotactic factor activates an amiloridesensitive Na/H countertransport which mediates an alkalinization of pH, via the net uptake of external Na in exchange for internal H.…”

mentioning

confidence: 89%

“…Considering the interrelationships between Na and H as dictated by Eq. 1, we were able to vary each of the four parameters independently in order to alter both the direction and magnitude of 1. Abbreviations used in this paper: DMO O2 under these conditions, we were able to correlate pH, responses with the degree of O2 generation and therefore, to de-termine the relationship of pHi to O2 production.…”

mentioning

confidence: 95%

See 1 more Smart Citation

Intracellular pH modulates the generation of superoxide radicals by human neutrophils.

Simchowitz¹

1985

J. Clin. Invest.

161

View full text Add to dashboard Cite

The relationship of intracellular pH (pH1) to superoxide radical (02) generation was investigated in chemotactic factor-stimulated human neutrophils. Exposure of cells to 100 nM N-formylmethionyl-leucyl-phenylalanine (FMLP) caused activation of Na/H exchange which, in 140 mM Na medium (pHo 7.40), led to a rise in pH1 from 7.22 to 7.80. This pH, change was sensitive to amiloride (apparent K1 78 MM), an inhibitor of Na/H countertransport. The time course of the alkalinization was similar to that of FMLP-stimulated 02 production, which was complete by 5 min. In the presence of 1 mM amiloride, which nearly blocked the pH, transient elicited by FMLP, or in the absence of external Na, where intracellular acidification was observed in FMLP-stimulated cells, 02-release was still roughly 25-45% of normal. Thus, an alkalinization cannot be an obligatory requirement for 02-generation. By independently varying either pH0, pH1, or the internal or external concentrations of Na, both the direction and magnitude of the FMLP-induced pH, transients could be altered. In each instance, the amount of 02-release correlated directly with pHi and was enhanced by intracellular alkalinization.In the absence of FMLP, a rise in pH, to 7.7-7.8 by exposure of cells to 30 mM NH4CI, 10 MM monensin (a Na/H exchanging ionophore), or after a prepulse with 18% CO2 did not result in 02 generation. Thus, these results imply that an alkalinization per se is not a sufficient trigger. Neutrophils exposed to 4 nM FMLP exhibited a threefold slower rate of alkalinization (reaching pHj 1 7.80 by 20-30 min) as compared to that obtained with 100 nM FMLP and did not release significant amounts of 02 under normal incubation conditions. However, these cells could be induced to generate 0°when the degree of alka tion was enhanced by internal Na depletion or by pretreatment with 18% Co2. Together, these results indicate a modulating effect of pH3 on 02 production and suggest that other functional responses of neutrophils may be regulated by their pH1.

show abstract

mentioning

confidence: 89%

mentioning

confidence: 95%

Intracellular pH modulates the generation of superoxide radicals by human neutrophils.

Simchowitz¹

1985

J. Clin. Invest.

161

View full text Add to dashboard Cite

show abstract

“…Only modest inhibition of degranulation by cyclic AMP was observed in peptone-elicited mouse peritoneal macrophages ingesting heat-aggregated gamma-globulin complexes (Welscher & Cruchaud, 1976) and this inhibition was paralleled by depressed phagocytosis. Nevertheless, cyclic AMP and cyclic GMP might in some circumstances exert mutually antagonistic controlling influences on phagolysosome formation in mouse peritoneal macrophages similar to those in other cells (Henson, 1974). If this were so, then antibody precoated on to tubercle bacilli might have promoted fusion by stimulating an unusually large synthesis of cyclic GMP, nullifying the postulated inhibitory effect of cyclic AMP.…”

mentioning

confidence: 98%

Phagosome-Lysosome Fusion and Cyclic Adenosine 3': 5'-Monophosphate in Macrophages Infected with Mycobacterium microti, Mycobacterium bovis BCG or Mycobacterium lepraemurium

Lowrie

Aber

Jackett

1979

Journal of General Microbiology

View full text Add to dashboard Cite

When ingested by mouse peritoneal macrophage monolayers, live Mycobacterium microti caused a sustained increase in monolayer cyclic AMP content and fusion of lysosomes with the bacterium-containing phagosomes was impaired. Ingested live M . bovis BCG caused a transient increase in cyclic AMP and the defect in phagolysosome formation was less pronounced. Dead mycobacteria and live M . lepraemurium neither enhanced monolayer cyclic AMP content nor inhibited phagolysosome formation, Mycobacterium microti and BCG exceeded M . lepraemurium in cyclic AMP-synthesizing activity in vitro but the question of whether bacterial cyclic AMP contributed substantially to the increments in infected macrophages was not resolved. Anti body-coated BCG retained the ability to synthesize cyclic AMP and to enhance monolayer cyclic AMP but lost the ability to inhibit phagolysosome formation in macrophages. The observations are discussed in terms of possible control of phagolysosome formation by cyclic nucleotides.

show abstract

“…Chemotactic stimuli have been shown to cause the selective release of the content of specific and gelatinase granules, while azurophil granules are retained unless cells are pretreated with cytochalasin B (9,10). We demonstrated that FMLP and calcium ionophore A23 187 induced the release of met-enkephalin-containing peptides without pretreatment with cytochalasin B.…”

Section: Resultsmentioning

confidence: 77%

Proenkephalin system in human polymorphonuclear cells. Production and release of a novel 1.0-kD peptide derived from synenkephalin.

Vindrola¹,

Padros²,

Sterin-Prync³

et al. 1990

J. Clin. Invest.

View full text Add to dashboard Cite

In the hematopoietic system a pluripotent stem cell generates precursors for lymphoid and myeloid lineages. Proenkephalinderived peptides were previously detected in differentiated lymphoid cells. We have studied whether the proenkephalin system is expressed in a typical differentiated cell of the myeloid lineage, the neutrophil. Human peripheral polymorphonuclear cells contain and release proenkephalin-derived peptides. The opioid portion of proenkephalin (met-enkephalincontaining peptides) was incompletely processed, resulting in the absence of low molecular weight products. The nonopioid synenkephalin (proenkephalin 1-70) molecule was completely processed to a 1.0-kD peptide derived from the COOH-terminal. This molecule was characterized in neutrophils by biochemical and immunocytochemical methods. The chemotactic peptide FMLP and the calcium ionophore A23187 induced the release of the proenkephalin-derived peptides, and this effect was potentiated by cytochalasin B. The materials secreted were similar to those present in the cell, although in the supernatant a higher proportion corresponded to more processed products. The 1.0-kD peptide was detected in human, bovine, and rat neutrophils, but the chromatographic pattern of synenkephalin-derived peptides suggests a differential posttranslational processing among species. These findings demonstrate the existence of the proenkephalin system in human neutrophils and the production and release of a novel 1.0-kD peptide derived from the synenkephalin molecule. The presence of opioid peptides in neutrophils suggests their participation in the inflammatory process, including a local analgesic effect. (J.

show abstract

Mechanisms of Mediator Release from Inflammatory Cells

Cited by 38 publications

References 91 publications

Intracellular pH modulates the generation of superoxide radicals by human neutrophils.

Intracellular pH modulates the generation of superoxide radicals by human neutrophils.

Phagosome-Lysosome Fusion and Cyclic Adenosine 3': 5'-Monophosphate in Macrophages Infected with Mycobacterium microti, Mycobacterium bovis BCG or Mycobacterium lepraemurium

Proenkephalin system in human polymorphonuclear cells. Production and release of a novel 1.0-kD peptide derived from synenkephalin.

Contact Info

Product

Resources

About