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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lang, F. Seidler, U. Wöll, E. Rossmann, H. Wiedermann, C. J. Lang, H. J. Kähler, C. M. Paulmichl, M. Reinisch, N. Zwierzina, H. Schratzberger, P. Seiler, K. Ritter, M. |
| Description | Author Affiliation: Ritter M ( Dept. of Internal Medicine, University of Innsbruck, Austria.) |
| Abstract | 1. Stimulation of chemotaxis of human polymorphonuclear leucocytes (PMNs) with the chemoattractive peptide fMLP (N-formyl-Met-Leu-Phe) is paralleled by profound morphological and metabolic alterations like changes of intracellular pH (pHi) and cell shape. The present study was performed to investigate the interrelation of cell volume (CV) regulatory ion transport, pHi and migration of fMLP stimulated PMNs. 2. Addition of fMLP to PMNs stimulated directed migration in Boyden chamber assays and was accompanied by rapid initial intracellular acidification and cell swelling. 3. Inhibition of the Na+/H+ exchanger suppressed fMLP stimulated cell migration, accelerated the intracellular acidification and inhibited the fMLP-induced cell swelling. 4. Step omission of extracellular Na+ caused intracellular acidification, which was accelerated by subsequent addition of gastric H+/K+ ATPase inhibitor SCH 28080, or by omission of extracellular K+ ions. In addition Na+ removal caused cell swelling, which was further enhanced by fMLP. 5. H+/K+ATPase inhibitors omeprazole and SCH 28080 inhibited stimulated migration and blunted the fMLP-induced increase in CV. 6. Increasing extracellular osmolarity by addition of mannitol to the extracellular solution caused cell shrinkage followed by regulatory volume increase, partially due to activation of the Na+/H+ exchanger. In fMLP-stimulated cells the CV increase was counteracted by simultaneous addition of mannitol. Under these conditions the fMLP stimulated migration was inhibited. 7. The antibacterial activity of PMNs was not modified by Hoe 694 or omeprazole. 8. Western analysis with a monoclonal anti gastric H+/K+ ATPase beta-subunit antibody detected a glycosylated 35 kD core protein in lysates of mouse and human gastric mucosa as well as in human PMNs. 9. The results indicate that fMLP leads to cell swelling of PMNs due to activation of the Na+/H+ exchanger and a K+-dependent H+-extruding mechanism, presumably an H+/K+ ATPase. Inhibition of these ion transporters suppresses the increase in CV and precludes PMNs from stimulated migration. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 124 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1998-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Chemotaxis, Leukocyte Drug Effects Gastric Mucosa Enzymology Neutrophils Proton Pump Inhibitors Sodium-Hydrogen Antiporter Antagonists & Inhibitors Animals Blood Bactericidal Activity Blotting, Western Cell Size Physiology Colony Count, Microbial Enzyme Inhibitors Pharmacology Escherichia Coli Growth & Development Cytology Metabolism Hydrogen-Ion Concentration In Vitro Techniques Intracellular Fluid Chemistry Ion Transport Mice Mice, Inbred C57BL Microscopy, Confocal N-Formylmethionine Leucyl-Phenylalanine Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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