Characterization of the Na+/HCO3-Cotransport in Human Neutrophils

Giambelluca, Miriam S.; Ciancio, María Carolina; Orlowski, Alejandro; Gende, Oscar A.; Pouliot, Marc; Aiello, Ernesto Alejandro

doi:10.1159/000358669

Cited by 12 publications

(10 citation statements)

References 29 publications

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“…This is also the only isoform in the choroid plexus where it is found to be apically localized (13). An ϳ119-kDa band was shown in a published Western blot from neutrophils, although it was described as 130 kDa (14). We occasionally found the 119-kDa isoform in the RPT, but more consistently found the 140-kDa band.…”

Section: Discussionmentioning

confidence: 69%

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The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions

Gildea

Carlson

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Section: Discussionmentioning

confidence: 69%

“…We generated human RPTC cell lines isolated from human kidney specimens as previously described (14). The cell lines have been extensively characterized using RPTC-specific markers (16).…”

Section: Human Renal Proximal Tubule Cell Culturesmentioning

confidence: 99%

The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions

Gildea

Carlson

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The intracellular pH of neutrophils is regulated by Na + /H + , Cl − /HCO 3 − antiporters, and Na + /HCO 3 − cotransporters . Shimizu et al.…”

Section: Resultsmentioning

confidence: 99%

Frontline Science: Aggregated neutrophil extracellular traps prevent inflammation on the neutrophil-rich ocular surface

Mahajan

Grüneboom

Petrů

et al. 2019

Journal of Leukocyte Biology

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Eye rheum is a physiological discharge, which accumulates at the medial angle of the healthy eye soon after opening in the morning. Microscopic evaluation of eye rheum revealed the presence of viable neutrophils, bacteria, epithelial cells, and particles, aggregated by neutrophil extracellular traps. We observed that in the evening, during eye closure, high C5a recruited neutrophils to the tear film and activated them. In this hypoxic area rich in CO2, neutrophils fight microbial aggressors by degranulation. Immediately after eye opening, the microenvironment of the ocular surface changes, the milieu gets normoxic, and loss of CO2 induces subtle alkalinization of tear film. These conditions favored the formation of neutrophil extracellular traps (NETs) that initially covers the ocular surface and tend to aggregate by eyelid blinking. These aggregated neutrophil extracellular traps (aggNETs) are known as eye rheum and contain several viable neutrophils, epithelial cells, dust particles, and crystals packed together by NETs. Similar to aggNETs induced by monosodium urate crystals, the eye rheum shows a robust proteolytic activity that degraded inflammatory mediators before clinically overt inflammation occur. Finally, the eye rheum passively floats with the tear flow to the medial angle of the eye for disposal. We conclude that the aggNETs‐based eye rheum promotes cleaning of the ocular surface and ameliorates the inflammation on the neutrophil‐rich ocular surfaces.

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“…Recently a Na + /HCO 3 − cotransporter has been identified (22, 23). Efflux of chloride is commonly accompanying activation of neutrophils (24).…”

Section: Discussionmentioning

confidence: 99%

Ménage-à-Trois: The Ratio of Bicarbonate to CO2 and the pH Regulate the Capacity of Neutrophils to Form NETs

et al. 2016

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In this study, we identified and characterized the potential of a high ratio of bicarbonate to CO2 and a moderately alkaline pH to render neutrophils prone to undergo neutrophil extracellular trap (NET) formation. Both experimental settings increased the rate of spontaneous NET release and potentiated the NET-inducing capacity of phorbol esters (phorbol-2-myristate-13-acetate), ionomycin, monosodium urate, and LPS. In contrast, an acidic environment impaired NET formation both spontaneous and induced. Our findings indicate that intracellular alkalinization of neutrophils in response to an alkaline environment leads to an increase of intracellular calcium and neutrophil activation. We further found that the anion channel blocker DIDS strongly reduced NET formation induced by bicarbonate. This finding suggests that the effects observed are due to a molecular program that renders neutrophils susceptible to NET formation. Inflammatory foci may be characterized by an acidic environment. Our data indicate that NET formation is favored by the higher pH at the border regions of inflamed areas. Moreover, our findings highlight the necessity for strict pH control during assays of NET formation.

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Characterization of the Na⁺/HCO₃^-Cotransport in Human Neutrophils

Cited by 12 publications

References 29 publications

The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions

The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions

Frontline Science: Aggregated neutrophil extracellular traps prevent inflammation on the neutrophil-rich ocular surface

Ménage-à-Trois: The Ratio of Bicarbonate to CO2 and the pH Regulate the Capacity of Neutrophils to Form NETs

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