Circulating Cell Populations Research Articles

Interleukin-18 stimulates hematopoietic cytokine and growth factor formation and augments circulating granulocytes in mice

Because interleukin-18 (IL-18) is similar to IL-1 and is known to be involved in the hematopoietic progenitor cell growth, the effect of IL-18 on circulating cell populations was examined. Repeated administration of IL-18 induced significant amounts of neutrophilia in mice. In parallel, high levels of interferon-gamma (IFN-gamma), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were detected in the serum of these mice. Interestingly, the cytokine profiles as well as the cell populations in circulation altered around 2 weeks after the beginning of IL-18 administration. A weak but definite eosinophilia was observed concurrently with the appearance of serum IL-5. Consistent with these observations, IL-18 induced secretion of IFN-gamma, GM-CSF, and IL-6 from splenocytes in culture. IL-18 also induced low levels of IL-5 in the splenocyte culture, which was inhibited by IL-12. However, markedly high levels of IL-5 were secreted into the culture medium when splenocytes from IFN-gamma-deficient mice were stimulated by IL-18. CD4(+) T cells strongly responded to IL-18 to secrete IL-5 and GM-CSF. IL-18 stimulated secretion of IL-6 and expression of G-CSF mRNA in splenic adherent cells. Expression of IL-18 receptors was detected in CD4(+) T cells and splenic adherent cells (macrophages). These results show that IL-18 stimulates CD4(+) T cells and macrophages to secrete IL-5, GM-CSF, IL-6, and granulocyte-colony stimulating factor in the absence of IL-12, which in turn induces hematopoietic cell proliferation causing neutrophilia and eosinophilia in mice.

T cells augment monocyte and neutrophil function in host resistance against oropharyngeal candidiasis.

The purpose of this study was to identify the cell populations involved in recovery from oral infections with Candida albicans. Monoclonal antibodies specific for CD4+ cells, CD8+ cells, and polymorphonuclear leukocytes were used to deplete BALB/c and CBA/CaH mice of the relevant cell populations in systemic circulation. Monocytes were inactivated with the cytotoxic chemical carrageenan. Mice were infected with 10(8) C. albicans yeast cells and monitored for 21 days. Systemic depletion of CD4+ and CD8+ T lymphocytes alone did not increase the severity of oral infection compared to that of controls. Oral colonization persisted in animals treated with head and neck irradiation and depleted of CD4+ T cells, whereas infections in animals that received head and neck irradiation alone or irradiation and anti-CD8 antibody cleared the infection in a comparable fashion. The depletion of polymorphonuclear cells and the cytotoxic inactivation of mononuclear phagocytes significantly increased the severity of oral infection in both BALB/c and CBA/CaH mice. High levels of interleukin 12 (IL-12) and gamma interferon (IFN-gamma) were produced by lymphocytes from the draining lymph nodes of recovering animals, whereas IL-6, tumor necrosis factor alpha, and IFN-gamma were detected in the oral mucosae of both naïve and infected mice. The results indicate that recovery from oropharyngeal candidiasis in this model is dependent on CD4+-T-cell augmentation of monocyte and neutrophil functions exerted by Th1-type cytokines such as IL-12 and IFN-gamma.

Are adhesion molecules involved in stress-induced changes in lymphocyte distribution?

Acute psychological stress is associated with important changes in circulating cell populations and reductions in cell-mediated immune responses. However, the mechanisms underlying these phenomena are poorly understood. In this study, we investigated (i) acute and chronic restraint stress effects in Sprague-Dawley rats on peripheral lymphocyte subsets and (ii) adhesion molecule (β2 integrins) expression and (iii) also determined whether glucocorticoids could underlie stress-related changes in cellular redistribution. We observed time-dependent changes in lymphocyte distribution including decreased (−21%) percentages of peripheral T helper cells and increased (88%) NK cell numbers following acute brief restraint. Acute stress was also found to overall upregulate β2-integrin (CD11a and CD11b) expression on T cells and to raise (1049%) plasma corticosterone levels. However, this stress response was found habituated (−75% vs. acute) in the animals previously exposed to chronic restraint stress. Stress effects on circulating lymphocytes were not observed in animals previously exposed to chronic intermittent restraint stress or chronically stressed animals re-exposed to the same stressor. Our results indicate that 1) stress alters lymphocyte distribution, 2) that adhesion molecules may be involved in stress-induced alterations of T-cell distribution and 3) that these changes may be related to circulating glucocorticoids and subjected to adaptation with repeated stress exposure.

Alternatives to human blood and blood resources.

Biotechnology is increasingly providing alternatives to established transfusion products, with the promise of freedom from infectivity and unlimited supply. Such products must demonstrate a safety and efficacy at least as great as current products, and thereafter an improved cost-benefit ratio. Alternatives to established products may be categorised as: Alternatives made from blood donations. Substitutes (acting by distinct mechanisms). Recombinant analogs. Cellular therapies (including gene therapy). This overview covers the current status in each of these categories, and likely trends in the near future. Recombinant therapeutic proteins are already established in certain indications, and are likely to be extended to a wider range of applications as the methods for bulk production are improved. Alternative products from donated blood should find niche indications, especially for acute therapy, but cellular therapy is unlikely to be widely implemented on this timescale, except as an adjunct in life-threatening indications. Substitutes are perhaps the most interesting category and are expected to have a major impact, particularly through the use of "proteins" to stimulate endogenous production of circulating cell populations.

Effects of initial ischemia/reperfusion injury on the transplanted kidney.

Effects of initial ischemia/reperfusion injury on the transplanted kidney.

Enhancement of antigen-induced bronchoconstriction after intravascular complement activation with cobra venom factor. Reversal by granulocyte depletion.

Our previous studies have demonstrated that activation of the C system with cobra venom factor (CVF) in a passively sensitized guinea pig results in an enhanced bronchoconstrictor response to Ag but not to other constrictor agents. Thus, our immediate goal was to determine the mechanism of the CVF-induced enhancement of the Ag-induced bronchoconstriction. Isolated airways from sensitized guinea pigs that had been treated with CVF responded normally to Ag. Because such a system lacks the normal circulating cell populations, we hypothesized that the CVF-induced enhancement of the Ag-induced bronchoconstriction was dependent on the presence of circulating white blood cells or platelets. Guinea pigs were depleted of circulating granulocytes, platelets, or both using specific antisera and the effect on the CVF-induced enhancement of the Ag-induced bronchoconstriction was determined. We found that CVF treatment did not result in an enhanced Ag-induced bronchoconstriction in guinea pigs depleted of either granulocytes or both granulocytes and platelets. However, the enhanced response was still apparent in guinea pigs depleted of just platelets. We investigated the effects of CVF itself and found that CVF treatment did not alter the number, or percentages, of different cell populations in the bronchoalveolar lavage, did not alter the protein or albumin content of the lavage fluid or the wet:dry ratio of the lung. In addition, CVF did not cause an increase in airway microvascular permeability as assessed by leakage of Evans blue. However, CVF did substantially increase granulocytes sequestered in the lung as measured by increased myeloperoxidase content. Thus, C activation by CVF results in an increase in neutrophils in the lung and an enhanced Ag-induced bronchoconstriction dependent on the presence of circulating granulocytes. These studies suggest that C activation and/or retention of granulocytes in the lung may be important in determining the severity of an Ag-induced bronchoconstriction.

C5a-induced bronchoconstriction: absence of a role of circulating white blood cells and platelets.

C5a causes an intense bronchoconstriction when injected intravenously into the guinea pig. The present study was designed to determine if circulating white blood cells or platelets were important target cells for the induction of bronchoconstriction on intravenous injection of C5a. To accomplish this, we examined the effect of C5a on numbers of circulating cells as well as the effect of depletion of various circulating cell populations on C5a-induced bronchoconstriction. Intravenous injection of C5a caused a precipitous drop in circulating granulocytes which preceded the maximum bronchoconstrictor response. The levels of circulating platelets and mononuclear cells were unchanged by intravenous injection of C5a. Depletion of either white blood cells or platelets did not significantly alter either the maximum bronchoconstrictor response to C5a or the time course of the response. Thus, these studies suggest that C5a-induced bronchoconstriction in the guinea pig is not dependent on an interaction of C5a with circulating white blood cells or platelets.

Cell-mediated immunity in Graves' disease: Evaluation by count of rosette-forming cells

Lymphocyte surface markers (using E active-, E total-, EA- and EAC-rosettes and membrane immunoglobulin assay) were examined in 34 clinically and biochemically euthyroid patients with Graves' ophthalmopathy, in 19 hyperthyroid patients with Graves' disease and exophthalmos (12 untreated and 7 treated), in 7 patients with inflammatory or malignant exophthalmos, and 74 control subjects. Results suggest that the percentage of T and B lymphocytes and EAC-rosette-forming cells in patients with Graves' disease was not significantly different from that observed in the controls. In contrast, EA-RFC seemed significantly involved ( P < 0·001) in pathogenesis or in tissue damage of ophthalmopathy. The ability of antithyroid agents to affect circulating cell populations (i.e. immunomodulator activity of methimazole) was also observed.

Production and fate of erythroid cells in anaemic Xenopus Laevis

Adult Xenopus laevis, rendered anaemic by phenylhydrazine injection, have been studied during the recovery from such anaemia. Electron microscopy of liver and spleen sections indicates that both of these organs are active in the phagocytosis and destruction of the old damaged red blood cells. May-Grunwald and Giemsa staining of liver and spleen cells following anaemia has been used to show that erythropoiesis also occurs in both liver and spleen, and this has been confirmed by electron-microscope studies of these organs. Cell counting and radiolabelling of the new population of circulating erythroid cells in the period following phenylhydrazine injection suggests that a sudden release of basophilic erythroblasts from liver and spleen is followed by mitosis of this new cell population in circulation, and that no further release of erythroid cells from these organs is likely until complete recovery has occurred.

Monocyte cellular function in asthmatic patients on alternate-day steroid therapy

Monocyte cellular function in 15 asthmatics on alternate-day steroid therapy (mean dose of prednisone, 45.4 ± 17.45 mg qod) was studied at 8 a.m. and noon after receiving an 8 a.m. steroid dose and at 8 a.m. the following day, and was contrasted to function in 16 healthy controls. Monocyte chemotaxis, bacterial killing and phagocytosis, and oil phagocytosis were not significantly altered by the steroid dose. On the other hand, all the patients experienced monocytopenia, lymphopenia, and neutrophilia 4 hr following the administration of steroid. The lack of functional impairment on this clinically relevant steroid regimen is consistent with the lack of serious infections seen in patients on such regimens. This study re-enforces the need to differentiate the effect of even small doses of steroid on circulating cell populations from direct effects on cell function which occur only with very high or frequent steroid dose regimens.