Regulation of intracellular pH in human neutrophils.

Simchowitz, L; Roos, Albert de

doi:10.1085/jgp.85.3.443

Cited by 147 publications

(121 citation statements)

References 62 publications

(103 reference statements)

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“…Cross-inhibition experiments (Figs. 5 and 6), on the one hand, indicate that a cytoplasmic alkalinization is not involved in the expression of activation-specific neoepitopes of ␤ 2 integrins and, on the other hand, suggest a role for the TNF-induced drop in Cl Ϫ i in the activation of the Na ϩ /H ϩ exchanger and thus in the control of cytoplasmic pH (51,52). It is worth remembering that, as opposed to the TNF-induced Cl Ϫ efflux, the Cl Ϫ efflux triggered by ␤ 2 integrin cross-linking is dependent on a rise in pH i (53), providing additional proof of the complexity of the mechanisms that control ion fluxes in PMN.…”

Section: Discussionmentioning

confidence: 99%

Role of Intracellular Chloride in the Reversible Activation of Neutrophil β2 Integrins: A Lesson from TNF Stimulation

Menegazzi

Busetto

Cramer

et al. 2000

The Journal of Immunology

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The process of β2 integrin activation, which enhances the interaction of these heterodimers with ligands, plays a crucial role in the adherence-dependent neutrophilic polymorphonuclear leukocytes’ (PMN) responses to TNF. Our previous observation, showing that a marked decrease of the high basal Cl− content (Cl−i) is an essential step in the TNF-induced activation of PMN, stimulated this study, which investigates the role of alterations of Cl−i in the activation of β2 integrins triggered by TNF. Here we show that TNF enhances the expression of activation-specific neoepitopes of β2 integrins, namely, epitope 24, a unique epitope present on all three leukocyte integrin α subunits, and epitope CBRM1/5, localized to the I domain on the α-chain of Mac-1 (CD11bCD18). Moreover, we demonstrate that the conformational changes underlying the expression of the neoepitopes are dependent on a drop in Cl−i because 1) inhibition of Cl−i decrease is invariably accompanied by inhibition of β2 integrin activation, 2) Cl−i decrease induced by means other than agonist stimulation, i.e., by placing PMN in Cl−-free buffers, activates β2 integrins, and 3) restoration of the original Cl−i levels is accompanied by deactivation of β2 integrins. We also show that Cl−i decrease is required for TNF-induced cytoplasmic alkalinization, but such a rise in pHi does not seem to be relevant for β2 integrin activation. The results of our study emphasize the role of Cl− as a new PMN “second messenger.”

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Section: Discussionmentioning

confidence: 99%

Role of Intracellular Chloride in the Reversible Activation of Neutrophil β2 Integrins: A Lesson from TNF Stimulation

Menegazzi

Busetto

Cramer

et al. 2000

The Journal of Immunology

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“…Chloride-dependence of the cell response to an acute alkaline (but not acid) load has been described in leukocytes (41). In addition, in canine proximal tubule cells, recovery from an alkaline load (induced by NH3) has been found to be chloride-dependent (42).…”

Section: Discussionmentioning

confidence: 99%

Regulation of cell pH by ambient bicarbonate, carbon dioxide tension, and pH in the rabbit proximal convoluted tubule.

Krapf¹,

Berry²,

Alpern³

et al. 1988

J. Clin. Invest.

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“…However, a fall in pH i ought to inhibit NBCe1-A (Fig. 3), either directly or indirectly by lowering [HCO 3 Ϫ ] i and [CO 3 2Ϫ ] i , just as a fall in pH i inhibits Cl-HCO 3 exchange in other cell types (37)(38)(39)(40).…”

Section: Do Proximal Tubules Sense Acute Phi Changes?mentioning

confidence: 99%

Evidence from renal proximal tubules that \documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation}{\mathrm{HCO}}_{3}^{-}\end{equation}\end{document} and solute reabsorption are acutely regulated not by pH but by basolateral \documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackag

Zhou

Zhao

Bouyer

et al. 2005

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

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Respiratory acidosis, a decrease in blood pH caused by a rise in [CO 2], rapidly triggers a compensatory response in which the kidney markedly increases its secretion of H ؉ from blood to urine. However, in this and other acid-base disturbances, the equilibrium CO 2 kidney ͉ out-of-equilibrium solution ͉ acid-base disturbances ͉ volume reabsorption A major task of the kidney is to secrete H ϩ into the urine.Inadequate renal H ϩ secretion caused, for example, by mutations to acid-base transporters (1-4) or carbonic anhydrases (5), or by renal failure (6, 7), can lead to a life-threatening decrease in blood pH. Moreover, to maintain a stable blood pH, the kidney must appropriately increase H ϩ secretion in response to metabolic acidosis (a decrease in blood pH caused by a decrease in [HCO 3 Ϫ ] at a fixed CO 2 ) or to respiratory acidosis. However, a half century after the classical observation that respiratory acidosis rapidly stimulates renal H ϩ secretion (8, 9), we still have little insight into how the kidney senses acute acid-base disturbances.The renal proximal tubule (PT) reabsorbs (from lumen to blood) a liquid that contains Ϸ80% of the HCO 3 Ϫ filtered by the glomerulus. The PT cell does this reabsorbtion by secreting H ϩ into the PT lumen and using this H ϩ to titrate luminal HCO 3 Ϫ to CO 2 and H 2 O. After entering the cell across the apical membrane, the CO 2 and H 2 O recombine to produce H ϩ and HCO 3 Ϫ . The cell extrudes the H ϩ into the lumen across the apical membrane through Na-H exchangers (10-12) and H ϩ pumps (13) and moves the HCO 3 Ϫ out across the basolateral membrane via the electrogenic Na͞HCO 3 cotransporter NBCe1-A (14, 15). Carbonic anhydrases catalyze the interconversions between CO 2 and H 2 O on the one hand and HCO 3 Ϫ and H ϩ on the other (5). Because blood pH is the parameter regulated by these acid-base transport processes, blood pH or, more likely, intracellular pH (pH i ), has been thought to be the parameter sensed by renal cells. However, because of the interconversion CO 2 ϩ H 2 O^HCO 3 In the present study, we perfused single, isolated S2 segments of rabbit PTs and collected the fluid that had passed along the PT lumen. Analysis of this collected fluid allowed us to compute volume reabsorption (J V ); HCO 3 Ϫ reabsorption (J HCO 3 ), which is virtually the same as the H ϩ -secretion rate under the conditions of our experiments; and the reabsorption of solutes other than NaHCO 3 (J Other ). We made the surprising observation that, at least in the short term, J HCO 3 and J Other do not respond to changes in basolateral or intracellular pH. The most straightforward hypothesis is that PT cells have sensors for basolateral HCO 3 Ϫ and a parameter related to CO 2 . Materials and MethodsExcept for the compositions of most of the OOE CO 2 ͞HCO 3 Ϫ solutions, our methods are described in detail in ref. 17.Tubule Perfusion. We hand dissected kidneys from ''pathogenfree'' female New Zealand White rabbits (1.4-2.0 kg) to yield individual segments of midcortical S2 PTs in accorda...

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Regulation of intracellular pH in human neutrophils.

Cited by 147 publications

References 62 publications

Role of Intracellular Chloride in the Reversible Activation of Neutrophil β2 Integrins: A Lesson from TNF Stimulation

Role of Intracellular Chloride in the Reversible Activation of Neutrophil β2 Integrins: A Lesson from TNF Stimulation

Regulation of cell pH by ambient bicarbonate, carbon dioxide tension, and pH in the rabbit proximal convoluted tubule.

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