Leukocyte Cell Types Research Articles

Age-related DNA methylation changes in peripheral whole blood

Aging is associated with many complex diseases such as cancer and neurodegenerative diseases. Recently, many age-related DNA methylation biomarkers in peripheral whole blood have been identified. These biomarkers may reflect DNA methylation changes derived from changes in the number of a specific leukocyte cell type during aging. To clarify the source of these age-related DNA methylation changes, we analysed DNA methylation profile of peripheral whole blood from three independent cohorts of healthy subjects and identified age-related DNA methylation CpG sites (arCpGs) using the Spearman's rank test with high reproducibility (Hypergeometric test, P=1.65 × 10⁻¹¹). Using a deconvolution algorithm, we found that the proportion of myeloid lineage cells was increased while that of lymphoid lineage cells was decreased in the peripheral whole blood with age (Spearman's rank correlation test, P<0.05, r ≤ 0.22). The CpG sites, whose methylation levels were significantly different in myeloid cells and lymphoid cells, were preferentially recognized as arCpGs in peripheral whole blood. Moreover, the arCpGs in CD4+ T cells significantly overlapped with that in peripheral whole blood (Hypergeometric test, P=6.14 × 10⁻¹²) and 99.1% of the overlapping arCpGs had consistent positive or negative correlations with age. Though the arCpGs in CD14+ monocytes did not significantly overlap with that in peripheral whole blood (Hypergeometric test, P=0.232), 90.1% of 51 overlapping arCpGs were correlated with age in CD14+ monocytes, peripheral whole blood, and CD4+ T cells consistently. In summary, most of the methylation changes in arCpGs identified in peripheral whole blood come from common or specific DNA methylation changes in leukocyte subtypes, while part of them reflect alterations in the number of specific cell types of leukocytes.

DETERMINATION OF SOME HAEMATOLOGICAL AND NON-SPECIFIC IMMUNE PARAMETERS IN NILE TILAPIA (Oreochromis niloticus L., 1758) FED WITH SPIRULINA (Spirulina platensis) ADDED DIETS

In this study, growth performance, haematological and non specific immune system parameters of Nile Tilap­ia ( Oreochromis niloticus L., 1758) fed with diets which contain different levels of (0; 5.0; 7.5 and 10.0 g/kg) spirulina ( Spirulina platensis ) were investigated. At the end of the feeding experiment (75 days), total erythrocyte (RBC) and leukocyte counts (WBC), hematocrit (Hct), hemoglobin (Hb), leukocyte cell types (monocyte, lymphocyte, neutrophil, eosinophyl), RBC indices (MCV, MCH, MCHC) and phagocytic activity of blood taken from fish were determined in a certain period. According to the results, the addition of 5.0 g/kg spirulina in diet highly increased the phago­cytic activity of neutrophils and monocytes and also the addition of 7.5 g/kg of spirulina in diet increased the amounts of RBC and WBC. Consequently, these two levels of spirulina can be used as a protective agent against diseases by support­ing the fish immune system.

Immune cell transcript modules reveal leukocyte heterogeneity in synovial biopsies of seronegative spondylarthropathy patients.

BackgroundThe objective of this study was to identify leukocyte cell types found within the synovia of patients with seronegative spondylarthropathies (SpA), such as ankylosing spondylitis (AS), using transcription based analyses.MethodsLeukocyte transcriptional profiles obtained from the NCBI’s gene expression omnibus and prediction analysis of microarrays (PAM) was used to identify 25-gene leukocyte metagenes. Subsequently, transcriptional profiles from murine and clinical models of AS and SpA were interrogated to characterize the local infiltration of leukocytes in SpA synovia.ResultsAnalysis of a proteoglycan-induced murine model of AS reveals infiltration of dendritic cells, CD4+ T cells, monocytes, and natural killer cells to the spine. In human SpA and AS patients, transcriptional analysis of synovial biopsies revealed local infiltration of dendritic cells and CD4+ T cells.ConclusionsWe identified leukocyte cell types that infiltrated the synovial of SpA patients. Our results imply a role for dendritic cells and CD4+ T cells in the local inflammation that underlies pathogenesis in patients with SpA.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-446) contains supplementary material, which is available to authorized users.

Genome‐wide DNA methylation in whole blood and CD16+ cells in response to chronic folic acid supplementation in women of child‐bearing age (817.1)

Folate is a key source of one‐carbon groups for DNA methylation; but studies on DNA methylation response to folic acid (FA) supplementation show inconsistent results. We hypothesize that measuring DNA methylation in whole blood (WB), which contains a mixture of distinct leukocyte cell types, may have confounded the results of previous studies. Therefore, the aim of this pilot study was to determine if a single cell type could serve as a more reliable epigenetic reporter. The study was performed in normal weight (BMI 18.5 – 24.9 kg/m2) women (18 – 35 y; n = 12), with blood samples taken before and after eight weeks of supplementation with 800 ug/day of FA. CD16+ cells (CD16) were isolated using antibody‐bound magnetic beads. DNA methylation patterns from WB and CD16 cells were measured across &gt;485,000 CpG sites using the Infinium Human Methylation450 Bead Chip. For each CpG site, the proportion of DNA methylation that changed over the 8 week intervention was evaluated by fitting a separate linear model. Genome‐wide analysis indicated changes in 7887 vs. 8482 CpG sites in response to supplementation in WB and CD16, respectively; with DNA methylation decreased in 77.2% (WB) or 66.3% (CD16) of these sites. Results suggest that there are differences in methylation response in WB and CD16 after FA supplementation. The implication of these methylation differences are being explored in our on‐going gene enrichment analyses.Grant Funding Source: Funded in part by HATCH #GEO00706, #GEO00707 and the Obesity Initiative at the University of Georgia

HY Immune Tolerance Is Common in Women without Male Offspring

BackgroundSex difference is an established risk factor for hematopoietic stem cell transplantation (HSCT)-related complications like graft versus host disease (GVHD). CD8pos cytotoxic T cells specific for Y chromosome-encoded minor Histocompatibility antigens (HY) play an important role therein. Prior to HSC donation, female donors may encounter HY antigens through fetomaternal or transmaternal cell flow, potentially leading to the induction of HY-specific cytotoxic or regulatory immune responses. Whether HY priming occurs independent of parity, and whether HY priming is dependent on the presence of male microchimerism, is as yet unknown.MethodsWe investigated the presence of HY-specific regulatory T cells (Treg) and male microchimerism in 45 healthy women with a fully documented pregnancy and family history. HY peptide-induced linked suppression, a commonly reported functional feature of CD4pos and CD8pos Treg, was measured by trans vivo Delayed Type Hypersensitivity testing. As source of HY antigens, male microchimerism was analyzed by real-time PCR and defined by the presence of male DNA in at least one purified leukocyte cell type.ResultsHLA class I or class II restricted HY-specific Treg were detected in 26/42 (62%) women eligible for analysis. The prevalence of HY-specific Treg was significantly higher in women who had never given birth to sons than in women with male offspring (p = 0.004). Male microchimerism could be detected in 24 out of 45 (53%) women but did not correlate with the presence of HY specific Treg.ConclusionsHY-specific Treg in women with male offspring have been described previously. Here we show for the first time that, in fact, HY specific Treg are more common in nulliparous women and in parous women with female offspring. Their presence is independent of the presence of male microchimerism. Whether HY-specific Treg presence in female stem cell grafts might decrease the GVHD incidence in male HSCT recipients needs to be investigated.

Testosterone implants modify the steroid hormone balance and the gonadal physiology of gilthead seabream (Sparus aurata L.) males

Androgens can induce complete spermatogenesis in immature or prepubertal teleost fish; however, many aspects of the role of androgens in adult teleost spermatogenesis remain elusive. We used the in situ forming microparticle (ISM) system containing 1mg of testosterone (T)/kg body weight (T-ISM) in a homogenous population of gilthead seabream at testicular involution stage to study in vivo the effects of T on the sex steroid hormone balance and on the physiology of the gilthead seabream gonad. The levels of T, 11-ketotestosterone (11KT) and 17β-estradiol (E2) in plasma, gonad and liver were determined in T-ISM implanted specimens after 7, 14, 21 and 28 days. The effect of T-ISM was evaluated on (i) de novo synthesis and metabolism of T in the gonad and liver by measuring the gene expression levels of the main steroidogenic proteins involved, (ii) the progress of spermatogenesis, (iii) the presence of different leukocyte cell types in the gonad, and (iv) the mRNA expression of some genes involved in the leukocyte migratory influx into the gonad and of some immune-relevant molecules. T-ISM implants promote an increase of T up to supra-physiological levels which induce a depletion of E2 levels and maintain the 11KT levels at physiological concentrations. The gene expression profile of some steroidogenic enzymes in gonad and liver ruled out the transformation of T into estrogenic compounds following T-ISM implantation. Moreover, androgens may also be involved in the leukocyte migratory influx, which occurred even when cytokine, chemokine and cell adhesion molecule gene expressions were down-regulated. Moreover, T-ISM implants block germ cell proliferation, although increased dmrt1 gene expression may prevent the complete depletion of germ cells in the gonad. Furthermore, T down-regulated the expression of several tlr genes, which may result in the inhibition of the immune response in the gonad through the impaired ability to recognize and respond to pathogens.

Infection-Induced Hematopoiesis: A Zebrafish Perspective

In response to infection, the bone marrow adjusts production of leukocyte cell types to fight off disease. In this issue of Cell Stem Cell, Hall etal. (2012) use the zebrafish model to show that nitric oxide (NO) production drives expansion of hematopoietic progenitors to produce more granulocytes.

Bacterial Invasion of Vascular Cell Types: Vascular Infectology and Atherogenesis

To portray the chronic inflammation in atherosclerosis, leukocytic cell types involved in the immune response to invading pathogens are often the focus. However, atherogenesis is a complex pathological deterioration of the arterial walls, where vascular cell types are participants with regards to deterioration and disease. Since other recent reviews have detailed the role of both the innate and adaptive immune response in atherosclerosis, herein we will summarize the latest developments regarding the association of bacteria with vascular cell types: infections as a risk factor for atherosclerosis; bacterial invasion of vascular cell types; the atherogenic sequelae of bacterial presence such as endothelial activation and blood clotting; and the identification of the species that are able to colonize this niche. The evidence of a polybacterial infectious component of the atheromatous lesions opens the doors for exploration of the new field of vascular infectology and for the study of atherosclerosis microbiome.

Activation of Neutrophils by Nanoparticles

The use of nanoparticles (NPs) has increased in the past few years in various fields, including defence, aerospace, electronics, biology, medicine, and so forth. and in applications such as diagnostic technology, bioimaging, and drug/gene delivery. Thus, human exposure to NPs and nanomaterials is unavoidable and will certainly expand in the future resulting in a growing interest in nanotoxicology, the study of toxicity of nanomaterials. A number of studies have reported the effects of NPs in respect to pulmonary inflammation by investigating in vitro activation of pulmonary cells with NPs and in vivo in a variety of models in which neutrophils appear to be the predominant leukocyte cell type in lungs and in bronchoalveolar lavages following inhalation or intratracheal instillation of NPs. Despite the fact that several studies have reported an increased number of neutrophils, the literature dealing with the direct activation of neutrophils by a given NP is poorly documented. This paper will summarize the current literature in this latter area of research and will end with a perspective view in which our laboratory will be involved in the following years.

MxA as biomarker for the activity of interferon-alpha in patients with chronic hepatitis: Measurement by flow cytometry

Background: The antiviral protein MxA is induced in leukocytes by type-I-interferons. An increased expression of MxA has been shown by means of PCR in patients with chronic hepatitis undergoing interferon-alpha therapy. Additionally, it has been demonstrated that the clinical response to interferon-alpha is correlated to the basal expression of MxA. Therefore, MxA has been proposed to serve as a marker for the bioactivity of interferon-alpha. We investigated the utility of flow cytometry (FACS) to measure the expression of MxA in different leukocyte cell types in patients with chronic hepatitis. Methods: The expression of MxA was determined in permeabilized whole blood samples by FACS analysis using a FITC-conjugated antibody (clone 383, An der Grub, Austria). The mean channel flourescence was determined after gating for neutrophils (PMN), monocytes (Mono) and lymphocytes (Lympho). Data are given as mean and standard deviation. Statistical analysis was done by t-test. Results: Blood samples were obtained from patients with chronic hepatitis B (CHB, n=7), chronic hepatitis C (CHC, n=10), CHC under treatment with interferon alpha (IFN, n=10), and healthy subjects (Contr., n=15). MxA expression was significantly increased in IFN (PMN: 15228, p&lt;0.0001; Mono: 34873, p&lt;0.0001; Lympho: 9220, p&lt;0.0001) but not in CHB (PMN: 355, p=0.37; Mono: 38 5, p=0.53; Lympho: 243, p=0.33) or CHC (PMN: 5430, p=0.54; Mono: 378, p=0.66; Lympho: 222, p=0.16), as compared to Contr. (PMN: 4632, Mono: 3610, Lympho: 234). Conclusion: Interferon alpha-treatment results in a marked upregulation of MxA expression in patients with CHC. FACS analysis may serve as a convenient method in routine laboratory diagnostics for the monitoring of therapy in patients with chronic viral hepatitis.

Effect of β Glucan on Haematology of Common Carp (Cyprinus Carpio) Infected by Ectoparasites

In this study, the effects of beta-glucan on haematological parameters of common carp, Cyprinus carpio, which were naturally infested with ecto-parasites were determined. In the experimental group, infested fish were fed with 0.3% beta-glucan containing pellets during thirty days. In control, infested fish were fed with fish pellets without beta-glucan. Blood samples were collected from each group after feeding. Mortality rates, haemoglobin (Hb) (g/dl), haematocrite (hct) (%), erythrocyte (RBC) (x10 6 /mm 3 ), leukocyte (WBC) (x10 3 /mm 3 ) amounts and leukocyte cell types (%) were determined. In comparison with the control group, Hct and WBC amounts were increased in the fish fed with beta glucan (P 0.05) for Hb and RBC amounts. Lymphocytes were decreased, while monocytes and neutrophils were increasing among the leukocyte cell types. Survival rate values were 91.12 and 77.78% for fish fed with β-1,3/1,6 glucan and the control group, respectively.

Influence of \beta-1,3/1,6 glucan applications on some non-specific cellular immune response and haematologic parameters of healthy Nile tilapia (Oreochromis niloticus L., 1758)

In this study, the effects of \beta-glucan administration at different dosages on non-specific immune response and haematological parameters in healthy Nile tilapia (Oreochromis niloticus L.) were investigated. Fish were fed with diets containing 0.5% and 0.1% glucan (experiment) and without glucan (control) for 2 weeks. After feeding for 2 weeks with 2 different dosages, erythrocyte (RBC), leukocyte (WBC), hematocrit (Hct), haemoglobin (Hb) amount, leukocyte cell types (percentage of lymphocyte, monocyte, neutrophil, eosinophil), the values of phagocytic activities, erythrocyte cell indexes (MCV and MCH) and blood cell sizes were determined. WBC and phagocytic activity amounts, percentages of lymphocyte and monocyte of fish fed with the diets containing 0.1% glucan were higher than 0.5% glucan and control groups (P < 0.05). RBC amount was found to be higher in the experimental groups than in the control group. There were no differences between groups in terms of Hb, Hct, MCV, MCH, neutrophil, eosinophil, and cell sizes values (P > 0.05).

Deconvolution of Blood Microarray Data Identifies Cellular Activation Patterns in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with a complex spectrum of cellular and molecular characteristics including several dramatic changes in the populations of peripheral leukocytes. These changes include general leukopenia, activation of B and T cells, and maturation of granulocytes. The manifestation of SLE in peripheral blood is central to the disease but is incompletely understood. A technique for rigorously characterizing changes in mixed populations of cells, microarray expression deconvolution, has been applied to several areas of biology but not to SLE or to blood. Here we demonstrate that microarray expression deconvolution accurately quantifies the constituents of real blood samples and mixtures of immune-derived cell lines. We characterize a broad spectrum of peripheral leukocyte cell types and states in SLE to uncover novel patterns including: specific activation of NK and T helper lymphocytes, relationships of these patterns to each other, and correlations to clinical variables and measures. The expansion and activation of monocytes, NK cells, and T helper cells in SLE at least partly underlie this disease's prominent interferon signature. These and other patterns of leukocyte dynamics uncovered here correlate with disease severity and treatment, suggest potential new treatments, and extend our understanding of lupus pathology as a complex autoimmune disease involving many arms of the immune system.

Determination of Leukocyte Cell Types in Some Cyprinidae Caught From Different Regions of Ceyhan River (Adana-Turkey)

This study was carried out in a agricultural, industrial, domestic and slaughterhouse discharging region (around Buyukmang?t Village) of Ceyhan River and just under the Dam’s crest of Aslanta? (Osmaniye) founded on the same river. In this study, levels of pollution indicator parameters of the water and their effects on amount and size of leukocyte cell types (lymphocyte,monocyte, neutrophil and eosinophil) were investigated in common carp (Cyprinus carpio L.,1758) and spotted barb (Capoeta barroisi Lortet, 1894). An increase in quantities and sizes of monocyte, neutrophil cells from leukocyte cells accepted as basic of defence systems of these fishes in region of discharging which was determined as polluted was seen at the end of the study, however any structural disorder was no observed in the cells.

Cellular Players and Role of Selectin Ligands in Leukocyte Recruitment in a T-Cell-Initiated Delayed-Type Hypersensitivity Reaction

Delayed-type hypersensitivity (DTH) reactions are characterized by a strong cellular infiltrate, including neutrophils, macrophages, and T lymphocytes. In all these cell types, both E- and P-selectin-dependent adhesion pathways play a significant role in recruitment into the inflamed skin. Accordingly, inhibition of selectin-mediated interactions (eg, by antibodies) results in impairment of acute DTH reactions. However, whether inhibition of a specific cell type is responsible for the anti-inflammatory effect or whether all leukocytes are affected remains unclear. To address this question, we used fucosyltransferase-VII knockout mice that lack functional selectin ligands as either donors or recipients in a DTH model elicited by Th1 cell and antigen transfer. We found that selectin-mediated adhesion is required by Th1 effector cells to enter the DTH reaction site and, additionally, to elicit the DTH reaction. On the other hand, elimination of selectin binding in the recipient's neutrophils and macrophages by use of fucosyltransferase-deficient mice receiving wild-type Th1 effector cells resulted in a strongly reduced infiltration of neutrophils and macrophages but unimpaired footpad swelling. These findings demonstrate a major role for both E- and P-selectin in the recruitment of different leukocyte cell types. However, only the presence of selectin ligands on T cells was critical for the inflammatory reaction. These findings reveal T cells as the predominant targets for selectin blockade that aim to suppress skin inflammation.

Effects of an oral superoxide dismutase enzyme supplementation on indices of oxidative stress, proviral load, and CD4:CD8 ratios in asymptomatic FIV-infected cats.

This study was designed to test the effect of antioxidant supplementation on feline immunodeficiency virus (FIV)-infected felines. Six acutely FIV-infected cats (> or =16 weeks post-inoculation) were given a propriety oral superoxide dismutase (SOD) supplement (Oxstrin; Nutramax Laboratories) for 30 days. Following supplementation, the erythrocyte SOD enzyme concentration was significantly greater in the supplemented FIV-infected group than the uninfected control group or the unsupplemented FIV-infected group. The CD4+ to CD8+ ratio increased significantly (0.66-0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats. Proviral load and reduced glutathione (GSH) levels in leukocyte cell types did not change significantly following supplementation. Antioxidant supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats. This result warrants further investigation with trials of antioxidant therapy in FIV-infected cats that are showing clinical manifestations of their disease, as well as in other feline patients where oxidative stress likely contributes to disease pathogenesis, such as diabetes mellitus and chronic renal failure.

Diversity of Denizens of the Atherosclerotic Plaque

The atherosclerotic plaque typically harbors cells of several lineages whose conversations, mediated by extracellular or cell surface–associated messengers, influence decisively the biology and clinical consequences of the lesion. Early vascular biology studies defined the resting state of the endothelium, characterized by the elaboration of antithrombotic and vasodilatory mediators. The activated endothelium recruits inflammatory leukocytes, favors clot accumulation, participates in angiogenesis, and can influence the behavior of subjacent smooth muscle cells in ways that favor atherogenesis and vasoconstriction (Figure). More recently, we have come to appreciate that the endothelial cell not only can exhibit a spectrum of functions, but that some may arise postnatally from bone marrow–derived precursors.1 Thus, the heterogeneity of endothelial cells depends not only on the mutability of their function but also on their origin. The diversity of endothelium depends not only on lineage but also location, with increasingly well-understood differences between arterial, microvascular, and venous endothelial cells. Figure. Heterogeneity of major cell types in atherosclerotic plaques. Vascular biologists have long recognized heterogeneity of endothelial cells and smooth muscle cells, now understood to result from local mediator milieu, biomechanical stimuli, and different embryological origins. Indeed, recent data suggest that both of these intrinsic vascular cell types can arise in postnatal life from bone marrow–derived precursors. Immunological dogma recognizes several T-cell populations, exemplified here by the Th1 and Th2 subsets, which on the balance exert opposing influences on atherogenesis. New data now establish the relevance to atherosclerosis and hyperlipidemia of monocyte heterogeneity. Monocytes that bear high levels of the markers Ly6c/Gr-1 and P-selectin glycoprotein ligand exhibit more proinflammatory functions than their …

The inflammatory chemokines CCL2 and CCL5 in breast cancer

A causal role was recently attributed to inflammation in many malignant diseases, including breast cancer. The different inflammatory mediators that are involved in this disease include cells, cytokines and chemokines. Of these, many studies have addressed the involvement and roles of the inflammatory chemokines CCL2 (MCP-1) and CCL5 (RANTES) in breast malignancy. While minimally expressed by normal breast epithelial duct cells, both chemokines are highly expressed by breast tumor cells at primary tumor sites, indicating that CCL2 and CCL5 expression is acquired in the course of malignant transformation, and suggesting that the two chemokines play a role in breast cancer development and/or progression. Supporting this possibility are findings showing significant associations between CCL2 and CCL5 and more advanced disease course and progression. Furthermore, studies in animal model systems have shown active and causative roles for the two chemokines in this disease. In line with the tumor-promoting roles of CCL2 and CCL5 in breast cancer, the two chemokines were shown to mediate many types of tumor-promoting cross-talks between the tumor cells and cells of the tumor microenvironment: (1) they shift the balance at the tumor site between different leukocyte cell types by increasing the presence of deleterious tumor-associated macrophages (TAM) and inhibiting potential anti-tumor T cell activities; (2) of the two chemokines, mainly CCL2 promotes angiogenesis; (3) CCL2 and CCL5 which are expressed by cells of the tumor microenvironment osteoblasts and mesenchymal stem cells play a role in breast metastatic processes. In addition, both chemokines act directly on the tumor cells to promote their pro-malignancy phenotype, by increasing their migratory and invasion-related properties. Together, the overall current information suggests that CCL2 and CCL5 are inflammatory mediators with pro-malignancy activities in breast cancer, and that they should be considered as potential therapeutic targets for the limitation of this disease.

Blood cell profile of six Mediterranean mariculture fish species

Summary The haematological profile and a description of the cell types from the peripheral blood of six Mediterranean fish species are presented. The highest haematocrit value was recorded in the saupe, Sarpa salpa (P < 0.001), the only herbivorous species, and which also lacked monocyte cells. Eosinophils were absent from the blood of the European sea bass Dicentrarchus labrax. White sea bream, Diplodus sargus and gilthead sea bream, Sparus aurata had statistically significantly high numbers of neutrophils and low numbers of lymphocytes (P < 0.001). The numbers of different leucocyte cell types were not influenced by sex or maturity stage in any species, although some variation in the maximum diameter of the cells was observed.

Position of power

Migrating leukocytes are “rear-wheel drive cells,” says Antonella Viola. Her group finds that mitochondria, the cell's engines, shift to the back of neutrophils to power cell movement, as revealed in Campello et al. (page 2879). Figure 1 A migrating leukocyte gets its rear in gear by shifting mitochondia (red) to its back end. Mitochondria can accumulate in regions of the cell with high energy demands, such as at the active growth cones of developing neurons and at the neuromuscular synapse. Viola and her team wondered whether mitochondria might also adopt a specific intracellular location in migrating cells. Leukocytes migrate to immunological battlegrounds in response to chemokines, and the team now shows that, in vitro, this chemotaxis is coupled with movement of mitochondria to the rear of the cell, known as the uropod. Although the leading edge of the leukocyte sends out exploratory protrusions as these cells migrate, the uropod contains both the adhesion machinery and the myosin motors essential for cell movement, explains Viola. The discovery that mitochondria also relocate to the uropod leads Viola to suggest that, in the mechanics of cell migration, the power comes from the push. Mitochondrial movement along microtubules requires the mitochondria to first divide into smaller, mobile units. By preventing this division, the team revealed that mitochondrial relocation to the uropod was not just coupled with, but necessary for, leukocyte migration. Boosting the mitochondrial energy production in these cells compensated for a lack of relocation, suggesting that mitochondrial movement was required for localizing ATP production at the uropod. Indeed, the team showed that inhibiting mitochondrial, but not cytoplasmic ATP production, reduced activation of myosin motors in the uropod but not elsewhere in the cell. In addition to various leukocytic cell types, migrating human breast cancer cells also relocate their mitochondria to the rear, the team found. This suggests that inhibiting the division of mitochondria, and thus their movement, might be a potential intervention strategy for preventing tumor metastasis.