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The spatial distribution of RhoA, Rac2 and Cdc42 in human neutrophils allows for sequential chemoattractant stimulation
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
2001 (engelsk)Inngår i: FEBS Letters, ISSN 0014-5793Artikkel i tidsskrift (Fagfellevurdert) Submitted
sted, utgiver, år, opplag, sider
2001.
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-13607OAI: oai:DiVA.org:liu-13607DiVA, id: diva2:21047
Tilgjengelig fra: 2001-05-25 Laget: 2001-05-25 Sist oppdatert: 2009-04-14
Inngår i avhandling
1. Towards a Refined Model of Neutrophil Motility
Åpne denne publikasjonen i ny fane eller vindu >>Towards a Refined Model of Neutrophil Motility
2001 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2001. s. 135
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 670
Emneord
human polymorphonuclear leukocytes. PMNL, neutrophils, neutrophil motility, N-formyl-Met-Leu-Phe
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-5142 (URN)91-7219-964-4 (ISBN)
Disputas
2001-05-04, Aulan, Adm. byggnad, ingång 16, Campus US, Linköpings universitet, Linköping, 13:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2001-05-25 Laget: 2001-05-25 Sist oppdatert: 2018-01-13bibliografisk kontrollert

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