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PubMed1995

Taurine deficiency in dissociated mouse cerebellar cultures affects neuronal migration.

The role of taurine in the process of neuronal migration was studied in a microwell cell culture system. Immunocytochemical analysis of the cellular composition of this culture system revealed the presence of the astrocytic marker GFAP in some structures such as the aggregates of neuronal bodies and in those cables used for migration, resembling what is described in vivo. The neuronal marker gamma-enolase stained practically all structures, including the aggregates and all cables. The intracellular taurine concentration was reduced by 60% in mouse cerebellar granule cells treated with a blocker of taurine transport, guanidinoethane sulfonate (GES). Under these conditions cell migration was markedly reduced to approximately 50% of that in untreated cultures. Both, taurine depletion and impairment of cell migration induced by GES were prevented by adding taurine to the culture medium. Taurine deficiency similarly affected different morphological parameters such as the number of cables suitable for neuronal migration as well as the number of migrating neurons. The number of aggregates of neuronal bodies was significantly increased, by about 30%, as a consequence of the reduced migration. Taurine alone did not exert any effect on the parameters evaluated. GES treatment of granule cells did not affect mitochondrial metabolism or K(+)-stimulated Ca(2+)-dependent [3H]-D-aspartate release. This suggests that the described effects of taurine deficiency were not due to an alteration of neuronal viability and that the action of GES was not simply due to unspecific and deleterious effects. These results are in agreement with those obtained in in vivo studies. This approach represents a useful model to investigate the role played by taurine in the process of neuronal migration.

Amino Acids↗
PubMed1990

The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans.

Three known genes guide circumferential migrations of pioneer axons and mesodermal cells on the nematode body wall. unc-5 affects dorsal migrations, unc-40 primarily affects ventral migrations, and unc-6 affects migrations in both directions. Circumferential movements still occur, but are misdirected whereas longitudinal movements are normal in these mutants. Pioneer growth cones migrating directly on the epidermis are affected; growth cones migrating along established axon fascicles are normal. Thus these genes affect cell guidance and not cell motility per se. We propose that two opposite, adhesive gradients guide circumferential migrations on the epidermis. unc-5, unc-6, and unc-40 may encode these adhesion molecules or their cellular receptors. Neurons have access to the basal lamina and the basolateral surfaces of the epidermis, but mesodermal cells contact only the basal lamina. These genes probably identify molecular cues on the basal lamina that guide mesodermal migrations. The same basal lamina cues, or perhaps related molecules on the epidermal cell surfaces, guide pioneer neurons.

Animals↗
PubMed1993

Eicosapentaenoic acid abolishes the proatherogenic effects of cholesterol: effects on migration of bovine smooth muscle and endothelial cells in vitro.

It is well known that vascular endothelial cell (EC) migration plays a major role in regeneration of the injured endothelium and also that smooth muscle cell (SMC) migration is the important step for atheromatous plaque formation. In the present study, we investigated the effects of cholesterol and eicosapentaenoic acid (EPA) on bovine carotid artery EC and SMC migration using the modified Boyden chamber technique. The migration activity of the cholesterol-enriched ECs loaded with cholesterol-rich liposomes was significantly suppressed, whereas that of the cholesterol-enriched SMCs was enhanced. Next, we examined the effects of EPA pretreatment on the migration of both cell types. When ECs and SMCs were treated with EPA (5 micrograms/ml) for 2 days, the EPA content increased from 0.55 +/- 0.04% to 11.72 +/- 0.19% and 1.22 +/- 0.09% to 9.69 +/- 0.07% in cellular phospholipids, respectively. Although pretreatment of the ECs with EPA caused a significant increase in serum-induced cell migration, pretreatment of SMCs had no effect. If both cell types were concomitantly pretreated with EPA and cholesterol-rich liposomes, EPA abolished the effects of cholesterol on the migration of both cell types, but did not affect the content of cholesterol in both cells. These data indicate the possibility that EPA counteracts the atherogenic effect of cholesterol on EC and SMC migration.

Animals↗
PubMed2005

SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration.

Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes. Because HGF has strong effects on the motility of keratinocytes and is produced by fibroblasts, HGF is thought to regulate keratinocyte migration during wound healing. However, the intracellular signaling mechanism of HGF-induced keratinocyte migration is poorly understood. In this report, we clarify the roles of STAT3 and SOCS/CIS family in HGF-induced keratinocyte migration. HGF activated STAT3 and strongly induced keratinocyte migration. Transfection with the dominant-negative mutant of STAT3 almost completely abolished HGF-induced keratinocyte migration and STAT3 phosphorylation. Next, we studied the mechanisms that regulate STAT3 phosphorylation. HGF enhanced the expression of SOCS3/CIS3 by sixfold within 1h, but had minimum effect on SOCS1/JAB expression. Transfection with SOCS3/CIS3 almost completely abolished HGF-induced STAT3 phosphorylation and keratinocyte migration, indicating that SOCS3/CIS3 acts as a negative regulator of HGF-induced keratinocyte migration. In conclusion, SOCS3/CIS3 regulates HGF-induced keratinocyte migration by inhibiting STAT3 phosphorylation.

Cell Movement↗
PubMed2005

Cyclic strain-mediated regulation of vascular endothelial cell migration and tube formation.

UNLABELLED: Hemodynamic forces exerted by blood flow (cyclic strain, shear stress) affect the initiation and progression of angiogenesis; however, the precise signaling mechanism(s) involved are unknown. In this study, we examine the role of cyclic strain in regulating bovine aortic endothelial cell (BAEC) migration and tube formation, indices of angiogenesis. Considering their well-documented mechanosensitivity, functional inter-dependence, and involvement in angiogenesis, we hypothesized roles for matrix metalloproteinases (MMP-2/9), RGD-dependent integrins, and urokinase plasminogen activator (uPA) in this process. BAECs were exposed to equibiaxial cyclic strain (5% strain, 1Hz for 24h) before their migration and tube formation was assessed by transwell migration and collagen gel tube formation assays, respectively. In response to strain, both migration and tube formation were increased by 1.83+/-0.1- and 1.84+/-0.1-fold, respectively. Pertussis toxin, a Gi-protein inhibitor, decreased strain-induced migration by 45.7+/-32% and tube formation by 69.8+/-13%, whilst protein tyrosine kinase (PTK) inhibition with genistein had no effect. siRNA-directed attenuation of endothelial MMP-9 (but not MMP-2) expression/activity decreased strain-induced migration and tube formation by 98.6+/-41% and 40.7+/-31%, respectively. Finally, integrin blockade with cRGD peptide and siRNA-directed attenuation of uPA expression reduced strain-induced tube formation by 85.7+/-15% and 84.7+/-31%, respectively, whilst having no effect on migration. CONCLUSIONS: Cyclic strain promotes BAEC migration and tube formation in a Gi-protein-dependent PTK-independent manner. Moreover, we demonstrate for the first time a putative role for MMP-9 in both strain-induced events, whilst RGD-dependent integrins and uPA appear only to be involved in strain-induced tube formation.

Adaptation, Physiological↗
PubMed2006

Enhanced intrinsic migration of aggressive breast cancer cells by inhibition of Rac1 GTPase.

Rac GTPases are known to play a crucial role in regulating cytoskeletal changes necessary for cell migration. Migration has been shown to be positively regulated by Rac in most cell types. However, there is also a large body of conflicting evidence in some other cell types with respect to the role of Rac in migration, suggesting that Rac GTPases regulate cell migration in a cell type-dependent manner. In the present study, we have characterized the effects of Rac1 GTPase inhibition on the migratory abilities of a number of breast cancer cell lines with differential degrees of tumorigenic and metastatic potentials. We show that Rac1 inhibition in non-metastatic (MCF-7, T-47D) or moderately metastatic (Hs578T) cell lines results in inhibition of migration, whereas in highly metastatic cell lines (MDA-MB-435, MDA-MB-231, and C3L5) Rac1 inhibition results in stimulation of migration. This stimulation of migration following Rac1 inhibition is also accompanied by the enhanced RhoA activity, suggesting a possible existence of a dominating role of RhoA over Rac1 in regulating intrinsic migration of the highly metastatic breast cancer cells.

Aminoquinolines↗
PubMed2006

Cell cycle progression is required for nuclear migration of neural progenitor cells.

In the developing brain, neural progenitor cells in the ventricular zone (VZ) show a typical migration pattern-interkinetic nuclear migration, in which nuclear position within the VZ is correlated with the cell cycle. However, the mechanisms underlying this regulation remain unclear. To clarify whether the cell cycle progression controls nuclear migration of neural progenitor cells, we determined whether chemically induced cell cycle arrest affected nuclear migration patterns in the VZ. Administration of 5-azacytidine (5AzC) or cyclophosphamide (CP) to pregnant mice induced cell cycle arrest in the fetal neural progenitor cells of the telencephalon: 5AzC induced G2/M-phase arrest, and CP induced S-phase arrest. We used 5-bromo-2'-deoxyuridine (BrdU) labeling to determine the position of the cell in the cell cycle and the nuclei within the VZ at the same time. Cells arrested in G2/M-phase stopped migrating in the inner area of the VZ. Cells arrested in S-phase stopped migrating in the outer area. These results indicate that nuclear position within the VZ was correlated with cell cycle phase, even when the cell cycle was disrupted, and that the nuclei of neural progenitor cells can migrate only when their cell cycle is going. Our results suggest that cell cycle regulators might control the machinery of migration through a common regulatory mechanism.

Animals↗
PubMedDate not supplied

Polarization and directed migration of murine neutrophils is dependent on cell surface expression of CD44.

The importance of CD44 in murine neutrophil chemotaxis was studied in a Zigmond chamber. WT neutrophils polarized more rapidly and more extensively than CD44-/- neutrophils, which showed slow random migration and reduced activation of RhoA. CD44+/- neutrophils polarized more slowly, formed fewer directionally polarized cells, and migrated more slowly than WT cells. Antibodies to CD44 decreased polarization of WT neutrophils and reduced directed migration but not migration speed, indicating that CD44 mediates chemotactic signaling and migration through different pathways, while a hyaluronate substratum markedly reduced both the speed and directed migration of WT cells. In contrast to macrophages, the level of cell surface CD44 in neutrophils was not affected by osteopontin expression and CD44 did not co-localize with osteopontin. In polarized neutrophils, CD44 was enriched in uropods while cortical actin was predominant at the leading edge. Thus, both polarization and directed migration of neutrophils are dependent on the expression of CD44 and its interaction with hyaluronan, which could modulate neutrophil migration into inflamed tissues.

Actins↗
PubMed2006

CXCL12 and C5a trigger cell migration via a PAK1/2-p38alpha MAPK-MAPKAP-K2-HSP27 pathway.

Cell migration is critical for many processes, such as angiogenesis, inflammation, development and wound healing, and is also involved in tumour progression and metastasis. Here we show that CXCL12, complement factor 5a (C5a), hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF)-BB, which stimulate cell migration, also activate p38alpha MAPK. Pharmacological inhibition of this protein kinase with SB 203580 or BIRB 0796, or the genetic ablation of p38alpha MAPK, blocked cell migration induced by the aforementioned chemo-attractants. Macrophages from mice lacking one or more of the other p38 MAPK isoforms showed normal cell migration in response to C5a. We also show that the activation of p38alpha MAPK in response to CXCL12 requires the p21-activated protein kinases (PAK)-1 and PAK-2. MAPKAP-K2 is a protein kinase that is activated by p38alpha MAPK. Reducing its expression using RNA interference blocked CXCL12-induced HeLa cell migration, while macrophages from mice that do not express MAPKAP-K2 failed to migrate in response to C5a. Moreover, RNA interference against the small heat shock protein 27 (HSP27), a physiological substrate of MAPKAP-K2, blocked the CXCL12-induced cell migration. These results demonstrate a general and essential role of the PAK-p38alpha MAPK-MAPKAP-K2-HSP27 signalling pathway in mediating the effects of chemotactic stimuli on cell migration.

Animals↗
PubMed2004

The inositol 1,4,5-trisphosphate receptor regulates epidermal cell migration in Caenorhabditis elegans.

Polarized migration and spreading of epithelial sheets is important during many processes in vivo, including embryogenesis and wound healing. However, the signaling pathways that regulate epithelial migrations are poorly understood. To identify molecular components that regulate the spreading of epithelial sheets, we performed a screen for mutations that perturb epidermal cell migration during embryogenesis in Caenorhabditis elegans. We identified one mutant (jc5) as a weak mutation in itr-1, which encodes the single inositol 1,4,5-trisphosphate receptor (ITR) in C. elegans. During the migration of the embryonic epidermis, jc5 embryos display defects including misdirected migration or premature cessation of migration. Cells that halt their migration have disorganized F-actin and display reduced filopodial protrusive activity at their leading edge. Furthermore, some filopodia formed by epidermal cells in itr-1(jc5) embryos exhibit abnormally long lifetimes. Pharmacological studies with the inositol 1,4,5-trisphosphate antagonist xestospongin C phenocopy these defects, confirming that ITR function is important for proper epidermal migration. Our results provide the first molecular evidence that movements of embryonic epithelial cell sheets can be controlled by ITRs and suggest that such regulation may be a widespread mechanism for coordinating epithelial cell movements during embryogenesis.

Animals↗
PubMed2004

Evidence for tension-based regulation of Drosophila MAL and SRF during invasive cell migration.

Cells migrating through a tissue exert force via their cytoskeleton and are themselves subject to tension, but the effects of physical forces on cell behavior in vivo are poorly understood. Border cell migration during Drosophila oogenesis is a useful model for invasive cell movement. We report that this migration requires the activity of the transcriptional factor serum response factor (SRF) and its cofactor MAL-D and present evidence that nuclear accumulation of MAL-D is induced by cell stretching. Border cells that cannot migrate lack nuclear MAL-D but can accumulate it if they are pulled by other migrating cells. Like mammalian MAL, MAL-D also responds to activated Diaphanous, which affects actin dynamics. MAL-D/SRF activity is required to build a robust actin cytoskeleton in the migrating cells; mutant cells break apart when initiating migration. Thus, tension-induced MAL-D activity may provide a feedback mechanism for enhancing cytoskeletal strength during invasive migration.

Actin Cytoskeleton↗
PubMed2005

Computer simulations and image processing reveal length-dependent pulling force as the primary mechanism for C. elegans male pronuclear migration.

A male pronucleus migrates toward the center of an egg to reach the female pronucleus for zygote formation. This migration depends on microtubules growing from two centrosomes associated with the male pronucleus. Two mechanisms were previously proposed for this migration: a "pushing mechanism," which uses the pushing force resulting from microtubule polymerization, and a "pulling mechanism," which uses the length-dependent pulling force generated by minus-end-directed motors anchored throughout the cytoplasm. We combined two computer-assisted analyses to examine the relative contribution of these mechanisms to male pronuclear migration. Computer simulation revealed an intrinsic difference in migration behavior of the male pronucleus between the pushing and pulling mechanisms. In vivo measurements using image processing showed that the actual migration behavior in Caenorhabditis elegans confirms the pulling mechanism. A male pronucleus having a single centrosome migrated toward the single aster. We propose that the pulling mechanism is the primary mechanism for male pronuclear migration.

Animals↗
PubMed2005

RuvA is a sliding collar that protects Holliday junctions from unwinding while promoting branch migration.

The RuvAB proteins catalyze branch migration of Holliday junctions during DNA recombination in Escherichia coli. RuvA binds tightly to the Holliday junction, and then recruits two RuvB pumps to power branch migration. Previous investigations have studied RuvA in conjunction with its cellular partner RuvB. The replication fork helicase DnaB catalyzes branch migration like RuvB but, unlike RuvB, is not dependent on RuvA for activity. In this study, we specifically analyze the function of RuvA by studying RuvA in conjunction with DnaB, a DNA pump that does not work with RuvA in the cell. Thus, we use DnaB as a tool to dissect RuvA function from RuvB. We find that RuvA does not inhibit DnaB-catalyzed branch migration of a homologous junction, even at high concentrations of RuvA. Hence, specific protein-protein interaction is not required for RuvA mobilization during branch migration, in contrast to previous proposals. However, low concentrations of RuvA block DnaB unwinding at a Holliday junction. RuvA even blocks DnaB-catalyzed unwinding when two DnaB rings are acting in concert on opposite sides of the junction. These findings indicate that RuvA is intrinsically mobile at a Holliday junction when the DNA is undergoing branch migration, but RuvA is immobile at the same junction during DNA unwinding. We present evidence that suggests that RuvA can slide along a Holliday junction structure during DnaB-catalyzed branch migration, but not during unwinding. Thus, RuvA may act as a sliding collar at Holliday junctions, promoting DNA branch migration activity while blocking other DNA remodeling activities. Finally, we show that RuvA is less mobile at a heterologous junction compared to a homologous junction, as two opposing DnaB pumps are required to mobilize RuvA over heterologous DNA.

Adenosine Triphosphatases↗
PubMed2007

Protein kinase C-delta regulates migration and proliferation of vascular smooth muscle cells through the extracellular signal-regulated kinase 1/2.

BACKGROUND: Smooth muscle cell (SMC) migration and proliferation are early and crucial events in the pathogenesis of intimal hyperplasia, the primary cause of restenosis after vascular intervention. We tested the hypothesis that protein kinase C-delta (PKCdelta), a ubiquitously expressed intracellular protein kinase, regulates vascular SMC proliferation and migration. METHODS: Exogenous PKCdelta was expressed in cultured SMCs via stable transfection or adenovirus-mediated gene transfer. Conversely, endogenous PKCdelta was inhibited by means of targeted gene deletion (gene knock-out). Cell proliferation and migration were determined by (3)H-thymidine incorporation and 24-well transwell assay, respectively. RESULTS: We isolated and examined three A10 SMC lines in which PKCdelta was stably transfected. Compared with cells that were transfected with an empty vector, cells transfected with PKCdelta exhibited reduced ability to proliferate. Moreover, PKCdelta transfection inhibited SMC migration toward platelet-derived growth factor-BB. Similar inhibitory effects on proliferation and migration were also observed when PKCdelta was introduced into primary aortic SMCs via an adenoviral vector. Interestingly, SMCs isolated from PKCdelta knockout mice also displayed decreased chemotaxis and proliferation compared with PKCdelta(+/+) littermates, suggesting a complex yet critical role for PKCdelta. We studied the mitogen-activated protein kinase extracellular signal-regulated kinases (ERK) 1/2 as a possible signaling pathway for PKCdelta's inhibitory effect. PKCdelta overexpression diminished ERK1/2 activity. Molecular restoration of ERK activation reversed the inhibitory effect of PKCdelta on SMC proliferation and migration. CONCLUSIONS: We demonstrate that although normal migration and proliferation is lessened in SMCs deficient in PKCdelta, its prolonged activation also diminishes those behaviors. This suggests a dual, critical role for PKCdelta in SMC proliferation and migration, and thus intimal hyperplasia and restenosis.

Animals↗
PubMed2007

Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2 expression through PI3-K/Akt and NF-kappaB pathways.

Inhibition of dendritic cell (DC) migration into tissues and secondary lymphoid organs is an efficient way to induce immunosuppression and tolerance. CCR7 and PGE(2) are critical for DC migration to secondary lymphoid organs where DC initiate immune response. Triptolide, an active component purified from the medicinal plant Tripterygium Wilfordii Hook F., is a potent immunosuppressive drug capable of prolonging allograft survival in organ transplantation by inhibiting T cell activation and proliferation. Considering the essential role in T cell tolerance of DC migration to secondary lymphoid organs, here we demonstrate that triptolide can significantly inhibit LPS-triggered upregulation of CCR7 expression and PGE(2) production by inhibiting cyclooxygenase-2 (COX-2) expression in DC, thus impairing DC migration towards CCR7 ligand CCL19/MIP-3betain vitro. Moreover, triptolide-treated DC display impaired migration into secondary lymphoid organs and in vivo administration of triptolide also inhibits DC migration. Further studies show that the triptolide-mediated inhibitory effects of LPS-induced activation of phosphatidylinositol-3 kinase (PI3-K)/Akt and nuclear NF-kappaB activation are involved in down-regulation of COX-2 and CCR7 expression resulting in impaired migration to secondary lymphoid organs of DC. Therefore, inhibition of DC migration through decreasing COX-2 and CCR7 expression via PI3-K/Akt and NF-kappaB signal pathways provides additional mechanistic explanation for triptolide's immunosuppressive effect.

Animals↗
PubMed2004

Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study.

Preferential migration of stem cells toward the site of a lesion is a highly desirable property of stem cells that allows flexibility in the site of graft implantation in the damaged brain. In rats with unilateral stroke damage, neural stem cells transplanted into the contralateral hemisphere migrate across to the lesioned hemisphere and populate the area around the ischaemic infarct. To date, the migration of neural stem cells in the damaged brain has been mainly inferred from snapshot histological images. In this study, we demonstrate that by pre-labelling neural stem cells with the bimodal contrast agent Gadolinium-RhodamIne Dextran [GRID, detectable by both magnetic resonance imaging (MRI) and fluorescent microscopy], the transhemispheric migration of transplanted neural stem cells contralateral to a stroke lesion can be followed in vivo by serial MRI and corroborated by subsequent histological analyses. Our results indicate that neural stem cells migrated from the injection tract mainly along the corpus callosum within 7 days of transplantation and extensively re-populated the peri-lesion area by 14 days following implantation. In contrast, neural stem cells transplanted into sham controls did not show any substantial migration outside of the injection tract, suggesting that the transcallosal migration observed in the stroke-lesioned animals is due to neural stem cells being attracted by the lesion site. In vivo tracking of the migration of neural stem cells responding to damage will greatly enhance our understanding of optimal transplantation strategies as well as how neural stem cells promote functional and anatomical recovery in neurological disorders.

Animals↗
PubMed2005

Is susceptibility to perceptual migration and fusion modality-specific or multimodal?

A previous paper reported high susceptibility to spatial migration (allochiria) of tactile stimuli in about 25% of healthy individuals (High Error subjects). When synchronous stimuli touched the two hands, if the unattended stimulus was temporally modulated when the attended one was not (and was thus more salient than the latter), it "migrated" to and fused with or replaced the stimulus on the attended hand. When subjects rated similarity of the attended stimulus accompanied by a distractor to each stimulus alone, scaling distributions tested against a sampling model showed most High Error subjects experienced fused stimuli, others experienced replacement and Low Error subjects experienced neither. We argued that these migrations are equivalent to allochiria and that this underlies neglect and extinction. This study assessed whether the individual difference is modality-specific or not. In auditory and visual equivalents of the tactile rating experiment, the difference between High and Low Error subjects was replicated in audition, but no migration occurred in vision. However, when two words were briefly presented visually before a mask with cued report of one, letter migrations to equivalent locations did occur and the individual difference was reproduced. This constitutes the first report of individual differences in auditory fusion and visual letter migration. Migration occurred in egocentric coordinates but apparently preserved structural homology. Different migration rates between the modalities paralleled relative salience of the unattended to the attended stimulus. The multimodality of the individual difference suggests that its source is supramodal, in deficient binding of perceptual content to location.

Adult↗
PubMed2003

Neutrophil migration in inflammation: nitric oxide inhibits rolling, adhesion and induces apoptosis.

There is controversy in the literature over whether nitric oxide (NO) released during the inflammatory process has a pro- or inhibitory effect on neutrophil migration. The aim of the present investigation was to clarify this situation. Treatment of rats with non-selective, NG-nitro-L-arginine (nitro), or selective inducible NO synthase (iNOS), aminoguanidine (amino) inhibitors enhanced neutrophil migration 6h after the administration of low, but not high, doses of carrageenan (Cg) or Escherichia coli endotoxin (LPS). The neutrophil migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was also enhanced by nitro or amino treatments. The enhancement of Cg-induced neutrophil migration by NOS inhibitor treatments was reversed by co-treatment with L-arginine, suggesting an involvement of the L-arginine/NOS pathway in the process. The administration of Cg in iNOS deficient (iNOS(-/-)) mice also enhanced the neutrophil migration compared with wild type mice. This enhancement was markedly potentiated by treatment of iNOS(-/-) mice with nitro. Investigating the mechanisms by which NOS inhibitors enhanced the neutrophil migration, it was observed that they promoted an increase in Cg-induced rolling and adhesion of leukocytes to endothelium and blocked the apoptosis of emigrated neutrophils. Similar results were observed in iNOS(-/-) mice, in which these mechanisms were potentiated and reverted by nitro and L-arginine treatments, respectively. In conclusion, these results suggest that during inflammation, NO released by either constitutive NOS (cNOS) or iNOS down-modulates the neutrophil migration. This NO effect seems to be a consequence of decreased rolling and adhesion of the neutrophils on endothelium and also the induction of apoptosis in migrated neutrophils.

Animals↗