scholarly journals Dissecting the inflammatory twitch in allergically inflamed mice

2016 ◽  
Vol 310 (10) ◽  
pp. L1003-L1009 ◽  
Author(s):  
Joshua J. Pothen ◽  
Matthew E. Poynter ◽  
Lennart K. A. Lundblad ◽  
Jason H. T. Bates
Keyword(s):  
Inflammatory Response ◽  
Refractory Period ◽  
Time Course ◽  
Lavage Fluid ◽  
Gm Csf ◽  
Refractory Periods ◽  
Sequence Of Events ◽  
Cell Counts ◽  
Airways Resistance ◽  
Predetermined Time

We have previously advanced the hypothesis that the allergic inflammatory response in the lungs occurs as a self-limited sequence of events that begins with the onset of inflammation and then resolves back to baseline over a predetermined time course (Pothen JJ, Poynter ME, Bates JH. J Immunol 190: 3510–3516, 2013). In the present study we tested a key prediction of this hypothesis, which is that the instigation of the allergic inflammatory response should be accompanied by a later refractory period during which the response cannot be reinitiated. We challenged groups of ovalbumin-sensitized BALB/c mice for 3, 14, 21 and 31 consecutive days with aerosolized ovalbumin. We measured airways responsiveness as well as cell counts and cytokines in bronchoalveolar lavage fluid after the final challenge in subgroups from each group. In other subgroups we performed the same measurements following rest periods and after a final single recall challenge with antigen. We determined that the refractory periods for GM-CSF, KC, and IL-5 are no longer than 10 days, while those for IFNγ and IL-10 are no longer than 28 days. The refractory periods for total leukocytes and neutrophils were no greater than 28 days, while that for eosinophils was more than 28 days. The refractory period for airways resistance was less than 17, while for lung elastance it was longer than 28 days. Our results thus demonstrate that the components of the allergic inflammatory response in the lung have finite refractory periods, with the refractory period of the entire response being in the order of a month.

scholarly journals Kinetics of committed and primitive blood progenitor mobilization after chemotherapy and growth factor treatment and their use in autotransplants

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3808-3814
Author(s):  
HJ Sutherland ◽  
CJ Eaves ◽  
PM Lansdorp ◽  
GL Phillips ◽  
DE Hogge
Keyword(s):  
Steady State ◽  
Growth Factor ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Time Course ◽  
Recovery Phase ◽  
High Dose ◽  
Gm Csf ◽  
Cell Counts ◽  
Cd34 Cells

Peripheral blood cells (PBCs) collected by leukapheresis after progenitor mobilization with chemotherapy and growth factors have been used successfully to replace marrow autografts in protocols requiring stem-cell support. Moreover, such transplants are often associated with more rapid recovery of blood cell counts than is routinely achieved with bone marrow. While conditions that mobilize colony-forming cells (CFCs) into the circulation are becoming increasingly well characterized, little information is available as to how these or other mobilizing treatments may influence the release of more primitive cells into the peripheral blood. To quantitate the peripheral blood content of such cells, we used the long-term culture-initiating cell (LTC-IC) assay, which detects a cell type that is able to produce progeny CFCs after a minimum of 5 weeks in cultures containing marrow fibroblasts. In this report, we present the findings on 21 patients who were transplanted over a 7-year period at our institution with PBCs alone. PBCs were collected in steady-state (n = 6) or during the recovery phase after high-dose cyclophosphamide (Cy; n = 15, nine with and six without additional growth factor administration). PBCs collected from another 11 patients given granulocyte colony-stimulating factor (G-CSF) were transplanted together with autologous marrow. Time-course studies of nine patients after Cy +/- granulocyte-macrophage CSF (GM-CSF) showed that CD34+ cells, CFCs, and LTC-ICs fell from normal to undetectable levels after Cy, and increased at the time of white blood cell (WBC) recovery: LTC-ICs to a mean of sixfold and CFCs to a mean of 26-fold higher than normal. The mean number of CD34+ cells, CFCs, and LTC-ICs present in the PBC harvest was twofold to 10-fold higher after mobilization than in steady-state collections; however, more than 2-log interpatient variability was observed. After PBC transplantation, the median time to a WBC count more than 10(9)/L was 12 days; polymorphonuclear leukocyte (PMN) count more than 0.5 x 10(9)/L, 15 days; and platelet count more than 20 x 10(9)/L, 17 days, although patients who received fewer than 1.5 x 10(5) CFCs/kg had a more than 50% chance of delayed count recovery (> 28 days). Patients who received Cy + GM-CSF-stimulated PBCs had more rapid and consistent platelet recoveries as compared with other groups receiving Cy mobilized or steady-state PBCs alone, and a rapid WBC recovery after Cy predicted a rapid WBC recovery after transplantation.

The Time Course of Preparation*

1967 ◽  
Vol 19 (3) ◽  
pp. 272-279 ◽  
Author(s):  
Paul Bertelson
Keyword(s):  
Visual Stimulus ◽  
Refractory Period ◽  
Time Course ◽  
Reaction Times ◽  
Warning Signal ◽  
High Time ◽  
Refractory Periods ◽  
Time Uncertainty ◽  
Order Of Magnitude ◽  
Choice Reaction Times

The time course of the adjustments triggered by a warning signal was studied by measuring choice reaction times (RTs) at different predictable foreperiods after such a signal. Before the warning signal, a high time uncertainty situation was created by imposing either a long constant foreperiod of 5 sec. or one varying in the range 1.5 to 5 sec. The warning signal was a click. Foreperiods ranging from 0 to 300 millisec. were used in different blocks of trials. The stimulus was the onset of one of two lamps calling for the pressing of one of two keys. A control condition, without click, was used also. RTs were found to decrease continuously when the forperiod was increased from 0 to 100-150 millisec. The click delivered simultaneously with the stimulus permitted reactions significantly faster than in the control condition. It is concluded (a) that the latency of preparation can be much shorter than the 2 to 4 sec. reported by Woodrow; (b) that the warning signal can be used as a time cue to start preparatory adjustments without starting a refractory period of the order of magnitude found in experiments with pairs of successive reactions, and thus that such refractory periods are not the inevitable cost of paying attention to a signal. There is also some suggestion that in this situation the click not only triggers preparatory adjustments, but also causes an immediate facilitation of the reaction to the visual stimulus.

scholarly journals CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Mathieu Blot ◽  
◽  
Marine Jacquier ◽  
Ludwig-Serge Aho Glele ◽  
Guillaume Beltramo ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Mitochondrial Dna ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Cd40 Ligand ◽  
Response Patterns ◽  
Alveolar Cell ◽  
Epithelial Lining Fluid ◽  
Gm Csf ◽  
Cell Counts

Abstract Background COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). Methods Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. Results COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations. Conclusion CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. Trial registration ClinicalTrials.gov, NCT03955887

288. The post-insemination inflammatory response in the ewe

2005 ◽  
Vol 17 (9) ◽  
pp. 121 ◽  
Author(s):  
J. L. Scott ◽  
N. Ketheesan ◽  
P. M. Summers
Keyword(s):  
Inflammatory Response ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Samples ◽  
Gm Csf ◽  
Reproductive Tissues ◽  
Cell Counts ◽  
Macrophage Colony ◽  
Uterine Body

Insemination causes an inflammatory response in the female reproductive tract of many species. The cytokine/leukocyte network initiated during this reaction is believed to enhance reproductive success.1 This study investigated the post-insemination inflammatory response in the ewe. Fifteen nonparous ewes were mated with the same ram for 1 h and their reproductive tracts were collected 3, 6, 18, 24 or 48 h later. Another fifteen ewes were used as controls. Tissue samples and luminal mucus were collected from 10 sites in each reproductive tract and stained with haematoxylin and eosin, Diffquik and immunohistochemically using a monoclonal CD68 antibody to quantify neutrophils, eosinophils and macrophages. Presence of interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated using immunohistochemistry and enzyme-linked immunosorbent assay. Neutrophils and macrophages increased in reproductive tissues following insemination. Mean cell counts in 1.5-mm2 tissue of mated (M) and control (C) ewes demonstrated a peak in neutrophils at 6–18 h post-insemination with significant differences (P < 0.05) between mated and controls in the posterior cervix (M = 23.7; C = 4.1) and uterine body (M = 34.5; C = 11.5). Macrophages peaked at 18–24 h with significant differences (P < 0.05) between mated and controls in the vagina (M=13.4; C = 4.6), posterior cervix (M = 10.4; C = 2.7), mid-cervix (M = 8.5; C = 3.0) and ipsilateral mid-uterine horn (M = 14.2; C = 7.9). Neutrophils increased in the lumen of the cervix and uterine body following insemination but macrophage numbers did not change. Insemination did not affect eosinophils. IL-8 and GM-CSF were detected in endometrial epithelial cells in mated and non-mated ewes. Highest concentrations of IL-8 were found in vaginal mucus. Small quantities of GM-CSF were detected in occasional mucus samples. No difference between mated and non-mated ewes was demonstrated for either cytokine. In conclusion, the post-insemination inflammatory reaction in the ewe involves an increase in neutrophils and macrophages in reproductive tissues, with neutrophils crossing the epithelium into the lumen. There was no apparent increase in IL-8 or GM-CSF in response to insemination. (1)Robertson SA et al. (1997) American Journal of Reproductive Immunology 37, 438–442.

Time course of neutrophil and macrophage elastinolytic activities in cigarette smoke-induced emphysema

1998 ◽  
Vol 275 (6) ◽  
pp. L1134-L1144 ◽  
Author(s):  
A. Felix Ofulue ◽  
Mary Ko ◽  
Raja T. Abboud
Keyword(s):  
Cigarette Smoke ◽  
Time Course ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Smoke Inhalation ◽  
Morphometric Data ◽  
Lung Macrophages ◽  
Cell Counts ◽  
Differential Cell

The aim of this study was to compare the time course of neutrophil and macrophage elastinolytic potentials in the lungs of rats exposed daily to cigarette smoke inhalation for 1–6 mo in relation to the onset and progression of cigarette smoke-induced emphysema. Normal room air-exposed rats served as controls. Morphometric data of lung histological sections showed evidence of emphysema lesions in the lungs of smoke-exposed rats at month 2 and continuing to month 6. Data of total and differential cell counts in bronchoalveolar lavage fluid and collagenase-dissociated lung showed an increased number of lung neutrophils at month 1 of smoke exposure, but this was reduced to control levels at months 2– 6. In contrast, an increased number of lung macrophages was evident in the smoke-exposed rats at month 2 of exposure and continued to month 6. Data of the elastinolytic activities of the neutrophils and macrophages, determined in [3H]elastin-coated culture wells, showed that the elastinolytic activity of lung neutrophils in the smoke-exposed rats was similar to that of the control air-exposed rats at months 1– 6 of exposure. In contrast, the elastinolytic activity of lung macrophages in the smoke-exposed rats was increased at month 2 of exposure and remained increased at month 6. Excessive in vivo lung elastin breakdown (judged by increased levels of elastin-derived peptides and desmosine in lavage fluid, determined immunologically) was observed in the smoke-exposed rats at months 2– 6 of exposure. These data indicate that the time course of increased macrophage-directed elastinolytic activity in the lung, not that of neutrophils, is more closely associated with the evolution of cigarette smoke-induced emphysema.

scholarly journals The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models

2013 ◽  
Vol 126 (3) ◽  
pp. 207-221 ◽  
Author(s):  
Gerrit John ◽  
Katrin Kohse ◽  
Jürgen Orasche ◽  
Ahmed Reda ◽  
Jürgen Schnelle-Kreis ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cigarette Smoke ◽  
Mouse Models ◽  
Inflammatory Cell ◽  
Biological Effects ◽  
Acute Inflammatory Response ◽  
Cell Recruitment ◽  
Gm Csf ◽  
Cell Counts ◽  
Inflammatory Cell Recruitment

COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases and particles, most often CS (cigarette smoke), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking, second hand (sidestream) smoke exposure severely affects respiratory health. These processes can be studied in vivo in models of CS exposure of mice. We compared the acute inflammatory response of female C57BL/6 mice exposed to two concentrations [250 and 500 mg/m3 TPM (total particulate matter)] of sidestream and mainstream CS for 3 days and interpreted the biological effects based on physico-chemical differences in the gas and particulate phase composition of CS. BAL (bronchoalveolar lavage fluid) was obtained to perform differential cell counts and to measure cytokine release. Lung tissue was used to determine mRNA and protein expression of proinflammatory genes and to assess tissue inflammation. A strong acute inflammatory response characterized by neutrophilic influx, increased cytokine secretion [KC (keratinocyte chemoattractant), TNF-α (tumour necrosis factor α), MIP-2 (macrophage inflammatory protein 2), MIP-1α and MCP-1 (monocyte chemoattractant protein-1)], pro-inflammatory gene expression [KC, MIP-2 and MMP12 (matrix metalloproteinase 12)] and up-regulated GM-CSF (granulocyte macrophage colony-stimulating factor) production was observed in the mainstream model. After sidestream exposure there was a dampened inflammatory reaction consisting only of macrophages and diminished GM-CSF levels, most likely caused by elevated CO concentrations. These results demonstrate that the composition of CS determines the dynamics of inflammatory cell recruitment in COPD mouse models. Different initial inflammatory processes might contribute to COPD pathogenesis in significantly varying ways, thereby determining the outcome of the studies.

scholarly journals Kinetics of committed and primitive blood progenitor mobilization after chemotherapy and growth factor treatment and their use in autotransplants

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3808-3814 ◽  
Author(s):  
HJ Sutherland ◽  
CJ Eaves ◽  
PM Lansdorp ◽  
GL Phillips ◽  
DE Hogge
Keyword(s):  
Steady State ◽  
Growth Factor ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Time Course ◽  
Recovery Phase ◽  
High Dose ◽  
Gm Csf ◽  
Cell Counts ◽  
Cd34 Cells

Abstract Peripheral blood cells (PBCs) collected by leukapheresis after progenitor mobilization with chemotherapy and growth factors have been used successfully to replace marrow autografts in protocols requiring stem-cell support. Moreover, such transplants are often associated with more rapid recovery of blood cell counts than is routinely achieved with bone marrow. While conditions that mobilize colony-forming cells (CFCs) into the circulation are becoming increasingly well characterized, little information is available as to how these or other mobilizing treatments may influence the release of more primitive cells into the peripheral blood. To quantitate the peripheral blood content of such cells, we used the long-term culture-initiating cell (LTC-IC) assay, which detects a cell type that is able to produce progeny CFCs after a minimum of 5 weeks in cultures containing marrow fibroblasts. In this report, we present the findings on 21 patients who were transplanted over a 7-year period at our institution with PBCs alone. PBCs were collected in steady-state (n = 6) or during the recovery phase after high-dose cyclophosphamide (Cy; n = 15, nine with and six without additional growth factor administration). PBCs collected from another 11 patients given granulocyte colony-stimulating factor (G-CSF) were transplanted together with autologous marrow. Time-course studies of nine patients after Cy +/- granulocyte-macrophage CSF (GM-CSF) showed that CD34+ cells, CFCs, and LTC-ICs fell from normal to undetectable levels after Cy, and increased at the time of white blood cell (WBC) recovery: LTC-ICs to a mean of sixfold and CFCs to a mean of 26-fold higher than normal. The mean number of CD34+ cells, CFCs, and LTC-ICs present in the PBC harvest was twofold to 10-fold higher after mobilization than in steady-state collections; however, more than 2-log interpatient variability was observed. After PBC transplantation, the median time to a WBC count more than 10(9)/L was 12 days; polymorphonuclear leukocyte (PMN) count more than 0.5 x 10(9)/L, 15 days; and platelet count more than 20 x 10(9)/L, 17 days, although patients who received fewer than 1.5 x 10(5) CFCs/kg had a more than 50% chance of delayed count recovery (> 28 days). Patients who received Cy + GM-CSF-stimulated PBCs had more rapid and consistent platelet recoveries as compared with other groups receiving Cy mobilized or steady-state PBCs alone, and a rapid WBC recovery after Cy predicted a rapid WBC recovery after transplantation.

scholarly journals Postoperative Rise of Circulating Mitochondrial DNA Is Associated with Inflammatory Response in Patients following Pancreaticoduodenectomy

2021 ◽  
pp. 1-7
Author(s):  
Niv Pencovich ◽  
Nadav Nevo ◽  
Roi Weiser ◽  
Ekaterina Bonder ◽  
Yoel Bogoch ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Inflammatory Response ◽  
Delayed Gastric Emptying ◽  
Clinical Course ◽  
Severe Trauma ◽  
Postoperative Fever ◽  
Postoperative Course ◽  
Cell Counts ◽  
White Blood Cell Counts ◽  
The Relationship

<b><i>Introduction:</i></b> Accumulation of plasma mitochondrial DNA (mtDNA) following severe trauma has been shown to correlate with the development of systemic inflammatory response syndrome (SIRS) and may predict mortality. Our objective was to investigate the relationship between levels of circulatory mtDNA following pancreaticoduodenectomy (PD) and the postoperative course. <b><i>Methods:</i></b> Levels of plasma mtDNA were assessed by real-time PCR of the mitochondrial genes <i>ND1</i> and <i>COX3</i> in 23 consecutive patients who underwent PD 1 day prior to surgery, within 8 h after surgery, and on postoperative day (POD)1 and POD5. The abundance of mtDNA was assessed relative to preoperative levels and in relation to parameters reflecting the postoperative clinical course. <b><i>Results:</i></b> When pooled for all patients, the circulating mtDNA levels were significantly increased after surgery. However, while a significant (at least &#x3e;2-fold and up to &#x3e;20-fold) rise was noted in 11 patients, no change in mtDNA levels was noted in the other 12 following surgery. Postoperative rise in circulating mtDNA was associated with an increased rate of postoperative fever until day 5, decreased hemoglobin and albumin levels, and increased white blood cell counts. These patients also suffered from increased rates of delayed gastric emptying. No significant differences were demonstrated in other postoperative parameters. <b><i>Conclusion:</i></b> Circulating mtDNA surge is associated with an inflammatory response following PD and may potentially be used as an early marker for postoperative course. Studies of larger patient cohorts are warranted.

scholarly journals Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiancheng Luo ◽  
Rui Liu ◽  
Kaili Qu ◽  
Guorong Liu ◽  
Min Hang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lavage Fluid ◽  
Surface Expression ◽  
Pulmonary Injury ◽  
Protective Mechanisms ◽  
Tnf Α ◽  
Anti Platelet Drug ◽  
G Protein Coupled ◽  
Very High ◽  
Masson Staining

Abstract Background Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist anti-platelet drug. Methods In our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using C57BL/6 mouse models. Results TdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF) (p < 0.001). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1β (p  < 0.01), IL-6 (p < 0.05), and TNF-α (p < 0.001). Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 (GPR17) induced by CLP (p < 0.001). Conclusion Our study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.

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