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Neutrophil leukocyte motility requires directed water influx
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
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2002 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, Vol. 71, no 2, 212-222 p.Article in journal (Refereed) Published
Abstract [en]

The ability of neutrophils to sense and move to sites of infection is essential for our defense against pathogens. For motility, lamellipodium extension and stabilization are prerequisites, but how cells form such membrane protrusions is still obscure. Using contrast-enhanced video microscopy and Transwell® assays, we show that water-selective aquaporin channels regulate lamellipodium formation and neutrophil motility. Addition of anti-aquaporin-9 antibodies, HgCl2, or tetraethyl ammonium inhibited the function(s) of the channels and blocked motility-related shape changes. On human neutrophils, aquaporin-9 preferentially localized to the cell edges, where N-formyl peptide receptors also accumulated, as assessed with fluorescence microscopy. To directly visualize water fluxes at cell edges, cells were loaded with high dilution-sensitive, self-quenching concentrations of fluorophore. In these cells, motile regions always displayed increased fluorescence compared with perinuclear regions. Our observations provide the first experimental support for motility models where water fluxes play a pivotal role in cell-volume increases accompanying membrane extensions.

Place, publisher, year, edition, pages
2002. Vol. 71, no 2, 212-222 p.
Keyword [en]
aquaporins, anti-aquaporin antibodies, microscopy, HgCl2
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-13606OAI: oai:DiVA.org:liu-13606DiVA: diva2:21046
Available from: 2001-05-25 Created: 2001-05-25 Last updated: 2013-09-26
In thesis
1. Towards a Refined Model of Neutrophil Motility
Open this publication in new window or tab >>Towards a Refined Model of Neutrophil Motility
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The ability of human polymorphonuclear leukocytes (PMNL; neutrophils), to sense and move to sites of infection is essential for our defense against pathogens. Cell motility is critically dependent on a dynamic remodeling of morphology. The morphological polarization toward chemoattractants, such as N-formyl-Met-Leu-Phe (fMLF), is associated with temporary extension and stabilization of lamellipodia in the direction of movement. The underlying mechanisms of cell motility are, however, still not entirely elucidated. It is therefore an urgent task to extend the present experimental evidence to give solid basis for a comprehensive model. Here it is shown that nitric oxide (NO) stimulates the morphological response of neutrophils, most likely due to transient increases in [Ca2+]i, following addition of NO-donors. This will, hypothetically, activate gelsolin and other actin filament severing proteins, leading to a subsequent decrease in filamentous actin. The incapability to efficiently turnover the actin filament network then blocks all motile activity. It is also shown that N-formyl peptide receptors on polarized neutrophils accumulate non-uniformly towards regions involved in motility. It is suggested that neutrophils use the asymmetric receptor distribution for directional sensing and sustained migration. A model for lamellipodium extension, where water fluxes play a pivotal role is presented. It is suggested that water fluxes through water-selective aquaporin (AQP) channels, contribute to the propulsive force for formation of various membrane protrusions and, thus, cell motility. It is well known that small G proteins of the Rho family GTPases play important roles in the intracellular signaling underlying cell motility. In morphologically polarized neutrophils it is shown that Cdc42, Rac2 and RhoA display spatially distinct distributions, which allows for sequential chemoattractant stimulation of neutrophil motility. The specific localizations of Rac2, Cdc42 and RhoA relative to each other and filamentous actin and fMLF receptors support the hypothesized order of activation and regulation of neutrophil cell motility. In conclusion, the detailed analysis of motility-related issues presented here provide new data allowing further refinement of previous models of neutrophil motility.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2001. 135 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 670
Keyword
human polymorphonuclear leukocytes. PMNL, neutrophils, neutrophil motility, N-formyl-Met-Leu-Phe
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-5142 (URN)91-7219-964-4 (ISBN)
Public defence
2001-05-04, Aulan, Adm. byggnad, ingång 16, Campus US, Linköpings universitet, Linköping, 13:00 (English)
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Available from: 2001-05-25 Created: 2001-05-25 Last updated: 2012-01-24Bibliographically approved

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Loitto, Vesa-MattiForslund, TonySundqvist, TommyMagnusson, Karl-EricGustafsson, Mikael

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