PRIMING OF NEUTROPHIL [Ca2+]i SIGNALING AND OXIDATIVE BURST BY HUMAN FRACTURE FLUIDS

Hauser, CJ; Desai, Nirav K.; Fekete, Zoltán; Livingston, DH; Deitch, E. A.

doi:10.1097/00005373-199901000-00061

Cited by 4 publications

(5 citation statements)

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“…Respiratory burst was measured spectrofluorometrically using an excitation wavelength of 488 nm and an emission wavelength of 530 nm. A detailed description can be found elsewhere [23]. Briefly, freshly isolated PMN (2ϫ10 6 cells/reaction) were applied into the cuvette containing DHR 123 (15 ng/ml).…”

Section: Pmn Respiratory Burstmentioning

confidence: 99%

Lysophosphatidic acid triggers calcium entry through a non-store-operated pathway in human neutrophils

Itagaki¹,

Kannan²,

Hauser³

2004

Journal of Leukocyte Biology

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Lysophosphatidic acid (LPA) is a bioactive lipid, which is structurally similar to sphingosine 1-phosphate (S1P) and which can mobilize Ca2+ in multiple cell types. We recently showed that S1P induces Ca2+ entry directly through store-operated Ca2+ entry (SOCE) channels in human polymorphonuclear neutrophils (PMN). We therefore examined the mechanisms by which LPA induces intracellular Ca2+ mobilization in PMN. External application of low micromolar LPA caused dose-dependent Ca2+ influx without releasing Ca2+ stores, whereas G-protein-coupled (GPC) LPA receptors respond to nanomolar LPA. Additive Ca2+ influx by LPA compared with 100 nM ionomycin-induced Ca2+ influx suggests that LPA-induced Ca2+ influx does not pass through SOCE channels. Ca2+ influx was resistant to inhibition of Gi/o by pertussis toxin, of phospholipase C by U73122, and of G12/13/Rho by Y27632, all demonstrating GPC receptor independence. This Ca2+ influx was inhibited by Gd3+, La3+, Zn2+, or MRS1845 but not by Ni2+ or the sphingosine kinase inhibitor dimethylsphingosine. In addition, we found that LPA has no effect on neutrophil chemotaxis; however, it has stimulatory effects on neutrophil respiratory burst in a dose-response manner. These findings suggest that LPA-induced Ca2+ influx in PMN occurs through a mechanism other than SOCE channels, independent of Ca2+ store-depletion and S1P synthesis, and that the characteristics of LPA-induced Ca2+ influx are similar to those of S1P-induced influx in terms of sensitivity to inorganic inhibitors. Unlike S1P, LPA has stimulatory effects on neutrophil respiratory burst.

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Section: Pmn Respiratory Burstmentioning

confidence: 99%

Lysophosphatidic acid triggers calcium entry through a non-store-operated pathway in human neutrophils

Itagaki¹,

Kannan²,

Hauser³

2004

Journal of Leukocyte Biology

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“…The value of these tests has been well established in a variety of disease processes. Marked differences have been observed in leukocyte CD11b expression (3–6) and oxidative burst response (7–9) between patients and healthy volunteers. However, empirical observations have suggested that considerable variability exists among individuals in the degree of oxidative burst and CD11b expression in leukocytes.…”

mentioning

confidence: 99%

Relationship between oxidative burst activity and CD11b expression in neutrophils and monocytes from healthy individuals: Effects of race and gender

et al. 2001

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Oxidative burst activity and the expression of adhesion molecules have been used as indicators of leukocyte activation status. The aim of the study was to delineate the relationship of oxidative burst activity and the expression of adhesion molecules in neutrophils and monocytes from a pool of healthy volunteers (n ‫؍‬ 96). We also tested the potential role of gender and a racial background in the individual response differences. Basal and phorbol myristate acetate (PMA)-stimulated oxidative burst and CD11b expression were determined using dihydrorhodamine 123 and phycoerythrin ( Key terms: neutrophils; monocytes; cell activation; flow cytometry; humanDetermination of oxidative burst and the expression of adhesion molecules by flow cytometry technique have been widely used in the assessment of leukocyte functional status (1,2). It has been accepted that oxidative burst activity and the expression of cell adhesion molecules parallel the activation status of neutrophils and macrophages. Elevated oxidative burst activity or CD11b expression indicates cell activation whereas decreased responses reflect downregulated cellular functions. The value of these tests has been well established in a variety of disease processes. Marked differences have been observed in leukocyte CD11b expression (3-6) and oxidative burst response (7-9) between patients and healthy volunteers. However, empirical observations have suggested that considerable variability exists among individuals in the degree of oxidative burst and CD11b expression in leukocytes. It is not known whether decreased (or augmented) responsiveness of oxidative burst is also manifested in a parallel decrease (or augmentation) in cell adhesion molecule expression. Furthermore, whereas ample evidence indicates that gender and age have major influences on leukocyte responses and on the host response to injury and infection (10 -12), the potential influence of ethnic background has not been investigated. Therefore, the aims of the study were to delineate the relationship between oxidative burst activity and expression of the CD11b adhesion molecule in neutrophils and monocytes from a representative pool of young healthy

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“…Although this mechanism was not investigated further, mechanical injury to vascular endothelial cells as a result of bone marrow and fragment emboli could lead to increased vascular congestion, permeability, and the accumulation of leukocytes in the pulmonary vessels. Systemically and locally, pulmonary neutrophil infiltration has been linked to the cytokine IL-8 23,24. Although not formally investigated, heightened levels of IL-8 seen in this study may be secondary to pulmonary vascular congestion and perivascular leukocyte infiltration (although the amount of marrow emboli was not quantified), which can be associated with long bone fracture or reperfusion.…”

Section: Discussionmentioning

confidence: 77%

“…In a pulmonary tissue injury model (lung reperfusion syndrome), elevation in IL-8 levels were associated with neutrophil infiltration into lung tissue and increased levels of neutrophils in bronchoalveloar lavage fluid, suggesting that IL-8 is a major mediator involved in neutrophil recruitment and neutrophil-dependent tissue damage 23. In addition to the pulmonary injury, fracture fluid (hematoma combined with fracture-generated cellular debris) released into circulation has been shown to contain significant levels of IL-8 and initiates the release of oxidative mediators (respiratory burst) within pulmonary tissue 24. Clinically, IL-8 levels have been shown to be elevated in traumatic deaths,7 but not in nontraumatic deaths, and serum levels at admission have been identified as the most important determinant of post-injury mortality in children following blunt trauma 8…”

Section: Discussionmentioning

confidence: 99%

Correlation of measurable serum markers of inflammation with lung levels following bilateral femur fracture in a rat model

Sears¹,

Volkmer²,

Yong³

et al. 2010

JIR

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IntroductionEvaluation of the systemic inflammatory status following major orthopedic trauma has become an important adjunct in basing post-injury clinical decisions. In the present study, we examined the correlation of serum and lung inflammatory marker levels following bilateral femur fracture.Materials and methods45 Sprague Dawley rats underwent sham operation or bilateral femoral intramedullary pinning and mid-diaphyseal closed fracture via blunt guillotine. Animals were euthanized at specific time points after injury. Serum and lung tissue were collected, and 24 inflammatory markers were analyzed by immunoassay. Lung histology was evaluated by a blinded pathologist.ResultsBilateral femur fracture significantly increased serum markers of inflammation including interleukin (IL)-2, IL-6, IL-10, GM-CSF, KC/GRO, MCP-1, and WBC. Femur fracture significantly increased serum and lung levels of IL-1a and KC/GRO at 6 hours. Lung levels of IL-6 demonstrated a trend towards significance. Histologic changes in pulmonary tissue after fracture included pulmonary edema and bone elements including cellular hematopoietic cells, bone fragments and marrow emboli.Discussion and conclusionOur results indicate that bilateral femur fracture with fixation in rats results in increases in serum markers of inflammation. Among the inflammatory markers measured, rise in the serum KC/GRO (CINC-1), a homolog to human IL-8, correlated with elevated levels of lung KC/GRO. Ultimately, analysis of serum levels of KC/GRO (CINC-1), or human IL-8, may be a useful adjunct to guide clinical decisions regarding surgical timing.

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PRIMING OF NEUTROPHIL [Ca2+]i SIGNALING AND OXIDATIVE BURST BY HUMAN FRACTURE FLUIDS

Cited by 4 publications

References 0 publications

Lysophosphatidic acid triggers calcium entry through a non-store-operated pathway in human neutrophils

Lysophosphatidic acid triggers calcium entry through a non-store-operated pathway in human neutrophils

Relationship between oxidative burst activity and CD11b expression in neutrophils and monocytes from healthy individuals: Effects of race and gender

Correlation of measurable serum markers of inflammation with lung levels following bilateral femur fracture in a rat model

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