Distribution Of Leukocyte Populations Research Articles

Effects of colchicine on lipolysis and adipose tissue inflammation in adults with obesity and metabolic syndrome.

The aim of this study was to examine whether colchicine's anti-inflammatory effects would improve measures of lipolysis and distribution of leukocyte populations in subcutaneous adipose tissue (SAT). A secondary analysis was conducted for a double-blind, randomized, placebo-controlled pilot study in which 40 adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. Non-insulin-suppressible (l0 ), insulin-suppressible (l2 ), and maximal (l0 +l2 ) lipolysis rates were calculated by minimal model analysis. Body composition was determined by dual-energy x-ray absorptiometry. SAT leukocyte populations were characterized by flow cytometry analysis from biopsied samples obtained before and after the intervention. Colchicine treatment significantly decreased l2 and l0 +l2 versus placebo (p < 0.05). These changes were associated with a significant reduction in markers of systemic inflammation, including high-sensitivity C-reactive protein, resistin, and circulating monocytes and neutrophils (p < 0.01). Colchicine did not significantly alter SAT leukocyte population distributions (p > 0.05). In adults with obesity and MetS, colchicine appears to improve insulin regulation of lipolysis and reduce markers of systemic inflammation independent of an effect on local leukocyte distributions in SAT. Further studies are needed to better understand the mechanisms by which colchicine affects adipose tissue metabolic pathways in adults with obesity and MetS.

Prenatal alcohol exposure is a risk factor for adult neuropathic pain via aberrant neuroimmune function

BackgroundClinical studies show that prenatal alcohol exposure (PAE) results in effects that persist into adulthood. Experimental animal models of moderate PAE demonstrate that young adults with PAE display potentiated sensitivity to light touch, clinically termed allodynia, following sciatic nerve chronic constriction injury (CCI) that coincides with heightened spinal glial, spinal macrophage, and peripheral immune responses. However, basal touch sensitivity and corresponding glial and leukocyte activation are unaltered. Therefore, the current study explored whether the enduring pathological consequences of moderate PAE on sensory processing are unmasked only following secondary neural insult.MethodsIn middle-aged (1 year) Long Evans rats that underwent either prenatal saccharin exposure (control) or moderate PAE, we modified the well-characterized model of sciatic neuropathy, CCI, to study the effects of PAE on neuro-immune responses in adult offspring. Standard CCI manipulation required 4 chromic gut sutures, while a mild version applied a single suture loosely ligated around one sciatic nerve. Spinal glial immunoreactivity was examined using immunohistochemistry. The characterization and functional responses of leukocyte populations were studied using flow cytometry and cell stimulation assays followed by quantification of the proinflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Data were statistically analyzed by ANOVA and unpaired t tests.ResultsThe current report demonstrates that mild CCI generates robust allodynia only in PAE rats, while the pathological effects of PAE following the application of a standard CCI are revealed by enhanced allodynia and elevated spinal glial activation. Additionally, mild CCI increases spinal astrocyte activation but not microglia, suggesting astrocytes play a larger role in PAE-induced susceptibility to aberrant sensory processing. Leukocyte populations from PAE are altered under basal conditions (i.e., prior to secondary insult), as the distribution of leukocyte populations in lymphoid organs and other regions are different from those of controls. Lastly, following in vitro leukocyte stimulation, only PAE augments the immune response to antigen stimulation as assessed by heightened production of TNF-α and IL-1β.ConclusionsThese studies demonstrate PAE may prime spinal astrocytes and peripheral leukocytes that contribute to enduring susceptibility to adult-onset neuropathic pain that is not apparent until a secondary insult later in life.

Decreased PD-1 Expression on CD8 Lymphocyte Subsets and Increase in CD8 Tscm Cells in Children with HIV Receiving Raltegravir.

We investigated the effect of combination antiretroviral therapy (cART) on immune recovery, particularly on the percentages of PD-1-positive cells within the major leukocyte subsets. Cryopreserved peripheral blood mononuclear cells and plasma samples collected longitudinally from a subset of 13 children and adolescents (between 9.7 and 18.2 years old) who were enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 were used for this study. Immunophenotyping by flow cytometry was performed to determine the effect of raltegravir-containing cART regimen on the distribution of leukocyte populations, on the expression of PD-1 on T cell subpopulations, and on the expression of well-established markers of T cell activation (CD38 and HLA-DR) on CD8 T cells. C reactive protein (CRP), lipopolysaccharide (LPS), IL-6, and soluble CD163 were assayed in plasma samples by an enzyme-linked immunosorbent assay. Plasma viral loads were decreased in all subjects (by an average of 2.9 log units). The cART regimen, including raltegravir, induced changes in CD8 T cell subsets, consistent with an effective antiretroviral outcome and improved immunologic status, including increased percentages of CD8 stem cell memory T cells (Tscm). The percentages of CD8 PD-1-positive cells decreased significantly as compared with baseline levels. Among the proinflammatory markers measured in plasma, sCD163 showed a decline that was associated with cART. cART therapy, including raltegravir, over 48 weeks in children is associated with immune restoration, consistent with effective antiretroviral therapy, namely decreased percentages of PD-1+ CD8+ T cells, an increase in CD8 Tscm cells, and decreased levels of sCD163.

The impact of mouse strain on iron ion radio-immune response of leukocyte populations

Purpose: Exposure to various forms of radiation, including iron ions that have an exceptionally high biological effectiveness, is an inevitable consequence of spaceflight. However, genetic background can significantly influence the response to radiation and hence also the overall health of crewmembers. The major goal of this study was to compare leukocyte population responses in two strains of mice that differ in susceptibility to radiation: C57BL/6 (resistant) and CBA/Ca (susceptible).Materials and methods: The mice were whole-body irradiated with 0, 50, 200, or 300 cGy 56Fe26 (1 GeV) at ∼1 Gy/min and euthanised on days 4 and 30 thereafter for analyses. Analyses included body and organ masses (spleen, liver, thymus, lungs), distribution of leukocyte populations in blood and spleen, red blood cell and platelet characteristics, expression of surface molecules (CD11b, CD54), and spontaneous and mitogen-induced blastogenesis.Results: There were main effects of Dose and Dose × Day interactions on virtually all quantified parameters in both strains of mice. In contrast, there were relatively few Dose × Strain and three-way interactions. Strain-related interactions involved changes in circulating phagocytic populations, erythrocytes, and liver mass.Conclusion: The data demonstrate that genetic background can modify certain immune-related parameters after exposure to heavy particle radiation. The possible implications of these findings are discussed.

Leukocyte Populations and mRNA Expression of Inflammatory Factors in Quarter Milk Fractions at Different Somatic Cell Score Levels in Dairy Cows

The effect of somatic cell count (SCC) and milk fraction on milk composition, distribution of cell populations, and mRNA expression of various inflammatory parameters was studied. Therefore, quarter milk samples were defined as cisternal (C), first 400g of alveolar (A1), and remaining alveolar milk (A2) during the course of milking. Quarters were assigned to 4 groups according to their total SCC: 1) <12×103/mL, 2) 12 to 100×103/mL, 3) 100 to 350×103/mL, and 4) >350×103/mL. Milk constituents of interest were SCC, fat, protein, lactose sodium, and chloride ions as well as electrical conductivity. Cell populations were classified into lymphocytes, macrophages, and neutrophils (PMN). The mRNA expression of the inflammatory factors tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, lactoferrin, and lysozyme was measured via real-time, quantitative reverse transcription PCR. Somatic cell count decreased from highest levels in C to lowest levels in A1 and increased thereafter to A2 in all groups. Fat content increased from C to A2 and with increasing SCC level. Lactose decreased with increasing SCC level but remained unchanged during milking. Concentrations of sodium and chloride, and electrical conductivity increased with increasing SCC but were higher in C than in A1 and A2. Protein was not affected by milk fraction or SCC level. The distribution of leukocytes was dramatically influenced by milk fraction and SCC. Lymphocytes were the dominating cell population in group 1, but the proportion of lymphocytes was low in groups 2, 3, and 4. Macrophage proportion was highest in group 2 and decreased in groups 3 and 4, whereas that of PMN increased from group 2 to 4. The content of macrophages decreased during milking in all SCC groups whereas that of PMN increased. The proportion of lymphocytes was not affected by milk fraction. The mRNA expression of all inflammatory factors showed an increase with increasing SCC but minor changes occurred during milking. In conclusion, milk fraction and SCC level have a crucial influence on the distribution of leukocyte populations and several milk constituents. The surprisingly high content of lymphocytes and concomitantly low mRNA expression of inflammatory factors in quarters with SCC <12×103/mL indicates a different and possibly reduced readiness of the immune system to respond to invading pathogens.

Uterine (CD56+) Natural Killer Cells Recruitment: Association with Decidual Reaction Rather than Embryo Implantation

Whether decidual leukocyte recruitment and/or increase is primarily hormonally regulated or induced mainly by blastocyst implantation is a matter of debate. Thus, this study investigated the number and distribution of leukocyte populations, with emphasis on natural killer (NK) cells of uterine and peripheral type, within decidual tissue from women with decidualized endometrium both related and unrelated to pregnancy and those with ectopic decidua associated with intrauterine pregnancy, as well as in tubal implantation sites. Immunohistochemical characterization of immune cells using antibodies to CD3, CD4, CD8, CD20, CD68, CD16, CD56, CD57, in formalin-fixed, paraffin-embedded tissue, and a quantitative analysis of these subpopulations was conducted in tissue blocks from four groups of patients: (i) 20 women with decidualized endometrium due to progestin therapy (i.e. not associated with gestation) (group Prog-D); (ii) 20 women with intrauterine pregnancy-associated ectopic decidua (seven in the Fallopian tube, five in the ovary, five in the uterine cervix, and three in the omentum) (group Ect-D); (iii) 20 women with spontaneous abortion who had an histologic sample of the decidua at the uterine implantation site (group Uter-D); and (iv) 20 consecutive patients who had had an ectopic tubal pregnancy (group Tub-Preg). Twenty gynecologic specimens with marked inflammatory reaction were used as controls (group Con). CD3+, CD4+, CD8+, CD68+ cells were detected in all tissue samples investigated. In contrast, CD20+ cells were detected in all samples in group Con, but only in 75%, 25%, 55% and 70% of groups Prog-D, Ect-D, Uter-D and Tub-Preg, respectively. In all tissue samples investigated, CD57+ and CD16+ cells were detected. Conversely, CD56+ cells were completely absent in 15 of 40 cases (37.5%) lacking decidual reaction (group Tub-Preg, 7/20; group Con, 8/20) but were present in all cases showing decidual reaction. In contrast with CD56+ cells, CD57+ NK cells were more abundant in group Con than in the four study groups. CD56+ NK cells are closely related to decidua irrespective of its eutopic or ectopic location rather than to the implantation site. This suggests that the recruitment and/or increase of uterine NK cells into the uterus is not dependent on the physical presence of an implanting embryo but instead is controlled hormonally.

Compartments within the lymph node cortex of calves and adult cattle differ in the distribution of leukocyte populations: An immunohistochemical study using computer-assisted morphometric analysis

The combination of an immunohistochemical technique and a panel of monoclonal antibodies was used to investigate the presence of leukocyte populations in the distal jejunal lymph node of 3–4 week old calves and adult cattle. The application of computer-assisted morphometric analysis enabled information to be obtained on the distribution of leukocyte populations in lymphoid compartments of the lymph node cortex. Semi-quantitative estimates of the areas of staining in histological sections showed that calves possessed significantly fewer B-cells and CD4+ cells in the outer cortex and significantly fewer T-cells (CD4+, CD8+ and γδ T-cells) in the deep cortex. These findings were interpreted to be a possible consequence of immunosuppression resulting from the passive transfer of maternal immunity in colostrum. The presence of some B-cell follicles in the region defined as the deep cortex suggested the on-going differentiation of this predominantly T-cell compartment. The larger presence of interdigitating cells (IDC) in the deep cortex of calves than adults was suggested by significantly larger CD1+ populations and it was argued that this could be the result of the confrontation with exogenous antigen faced by calves in early postnatal life. Antigen presenting populations, pan MHC II + and MHC II DQ + populations, were increased in all compartments of calf lymph nodes but were not significantly different from the populations in adult lymph nodes. Variance component analysis of the data generated in the present study showed that the image analysis technique was an effective and statistically powerful approach to investigate leukocyte populations within the specific microenvironments of the lymph node.