Dataset Information

Pro-haemostatic effect of DDAVP is partially derived through non-classical (CD14^dim /CD16⁺⁺ ) monocytes residing the spleen.

ABSTRACT: The splenic endothelial Weibel-palade bodies are one of the most important candidate organelles to release von Willebrand factor upon stimulation with desmopressin. However, the presence of functional desmopressin-specific receptor has not yet been demonstrated on endothelial cells. Experimental evidences are in favour of an indirect pro-haemostatic effect of desmopressin, but the exact mediator and its cellular origin are largely elusive. Here, we report partially hampered desmopressin response in a splenectomised severe haemophilia A/Beta Thalassemia patient without any genetic variant relevant to his incomplete desmopressin response. To further investigate the role of the spleen in this phenomenon, the release of VWF from desmopressin-treated human splenic endothelial cells was assessed in vitro. As a result, desmopressin induced the release of VWF from endothelial cells when the cells were co-cultured with non-classical (CD14^dim /CD16⁺⁺ ), but not other subtypes of monocytes or PBMCs. This in vitro study which resembles close proximity of endothelial cells of sinusoids to monocyte reservoir reside in parenchyma of subcapsular red pulp of the spleen sheds a light upon the role of this highly vascularized VWF-producing organ in driving indirect effect of desmopressin.

SUBMITTER: Salarilak L

PROVIDER: S-EPMC9806299 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Pro-haemostatic effect of DDAVP is partially derived through non-classical (CD14<sup>dim</sup> /CD16<sup>++</sup> ) monocytes residing the spleen.

Salarilak Laleh L Pirdel Zahra Z Dinmohammadi Hossein H Rokni-Zadeh Hassan H Lavend'homme Renaud R Karimi Mehran M Jacquemin Marc M Shahani Tina T

Journal of cellular and molecular medicine 20221207 1

The splenic endothelial Weibel-palade bodies are one of the most important candidate organelles to release von Willebrand factor upon stimulation with desmopressin. However, the presence of functional desmopressin-specific receptor has not yet been demonstrated on endothelial cells. Experimental evidences are in favour of an indirect pro-haemostatic effect of desmopressin, but the exact mediator and its cellular origin are largely elusive. Here, we report partially hampered desmopressin response ...[more]

PMID: 36479816

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Project description:BackgroundEvidence on the changes in the absolute counts of monocyte subpopulations in sepsis is missing.MethodsFirstly, absolute counts of circulating CD14pos/HLA-DRpos/CD45pos monocytes were measured by flow cytometry in 70 patients with Gram-negative sepsis and in 10 healthy volunteers. In the second phase, immunophenotyping was performed and the absolute count of circulating inflammatory monocytes and of circulating CD14dim/CD16pos/CD45pos patrolling monocytes were measured in another 55 patients and 10 healthy volunteers. Measurements were repeated on days 3, 7, and 10. Results were correlated with survival after 28 days.ResultsGreater numbers of CD14pos/HLA-DRpos/CD45pos monocytes were found on day 1 in survivors compared to nonsurvivors (p = 0.030). Receiver operating characteristic (ROC) analysis showed that a cutoff higher than 337 cells/mm3 on day 1 could discriminate between survivors and nonsurvivors with a positive predictive value (PPV) of 91.1%. Logistic regression including Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE) II score showed that an absolute count greater than 337 cells/mm3 was independently associated with unfavorable outcome (odds ratio (OR) 0.19, p = 0.050). The absolute counts of inflammatory and of CD14dim/CD16pos/CD45pos monocytes were greater in patients than healthy controls during the entire 10 days of follow-up. The absolute counts on day 3 of CD14dim/CD16pos/CD45pos monocytes were greater in survivors than nonsurvivors (p = 0.027). ROC analysis revealed that the cutoff at 27 cells/mm3 could discriminate between survivors and nonsurvivors with PPV of 94.1%. Logistic regression including age, SOFA score, and APACHE II score showed that an absolute count greater than 27 cells/mm3 was independently associated with unfavorable outcome (OR 0.06, p = 0.033). Logistic regression analysis showed that intra-abdominal infection on day 1 was predictive of low CD14dim/ CD16pos/CD45pos count on day 3.ConclusionCirculating counts of inflammatory and patrolling monocytes are greatly increased in Gram-negative sepsis. Absolute counts of CD14pos/HLA-DRpos/CD45pos monocytes on day 1 and CD14dim/CD16pos/CD45pos monocytes on day 3 are independently associated with final outcome.Trial registrationClinicalTrials.gov, NCT01223690 . Registered retrospectively on 18 October 2010.

Dataset Information

Pro-haemostatic effect of DDAVP is partially derived through non-classical (CD14^dim /CD16⁺⁺ ) monocytes residing the spleen.

Publications

Pro-haemostatic effect of DDAVP is partially derived through non-classical (CD14<sup>dim</sup> /CD16<sup>++</sup> ) monocytes residing the spleen.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Pro-haemostatic effect of DDAVP is partially derived through non-classical (CD14dim /CD16++ ) monocytes residing the spleen.

Publications

Pro-haemostatic effect of DDAVP is partially derived through non-classical (CD14<sup>dim</sup> /CD16<sup>++</sup> ) monocytes residing the spleen.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Pro-haemostatic effect of DDAVP is partially derived through non-classical (CD14^dim /CD16⁺⁺ ) monocytes residing the spleen.