Recent Advances in the Discovery and Development of CCR1 Antagonists

Zhang, Penglie; Dairaghi, Daniel J.; Jaén, Juan C.; Powers, Jay P.

doi:10.1016/b978-0-12-417150-3.00010-7

Cited by 8 publications

(4 citation statements)

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“…Platelets mediate the recruitment of monocytes and macrophages through the release of PF4, which induces the migration of C–C chemokine receptor type 1 (CCR1)-expressing cells. CCR1 promotes inflammation because it regulates the traffic of immune effector cells when binding to its ligands ( 20 , 21 ); this pathway suggests a link between an inflammatory environment and PF4 ( 22 ). Currently, it is uncertain how platelet activation impacts monocyte activation and inflammation status during LTB and ATB.…”

Section: Introductionmentioning

confidence: 99%

High levels of PF4, VEGF-A, and classical monocytes correlate with the platelets count and inflammation during active tuberculosis

et al. 2022

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Platelets play a major role in coagulation and hemostasis; evidence supports the hypothesis that they also contribute to immunological processes. Increased platelet counts have been associated with poor prognosis in tuberculosis (TB). Platelet–monocyte aggregates have been reported in patients with TB, but it is still unclear if only one monocyte subpopulation is correlated to the platelet count; moreover, the platelet–monocyte axis has not been studied during latent tuberculosis (LTB). In this study, mononuclear cells and plasma were obtained from patients diagnosed with active drug-sensitive TB (DS-TB, n = 10) and LTB (n = 10); cytokines and growth factors levels associated to platelets were evaluated, and correlations with monocyte subpopulations were performed to identify a relationship between them, as well as an association with the degree of lung damage. Our data showed that, compared to LTB, DS-TB patients had an increased frequency of platelets, monocytes, and neutrophils. Although DS-TB patients showed no significant difference in the frequency of classical and non-classical monocytes, the classical monocytes had increased CD14 intensity of expression and frequency of TLR-2+. Furthermore, the plasma levels of angiogenic factors such as vascular endothelial growth factor (VEGF-A), platelet-derived growth factor (PDGF-BB), and platelet factor-4 (PF4), and pro-inflammatory cytokines like interleukin 6 (IL-6), interleukin 1 beta (IL-1β), and interferon-γ-inducible protein 10 (IP-10) were increased in DS-TB patients. In addition, PF-4 and VEGF-A correlated positively with the frequency of classical monocytes and the platelet count. Using a principal component analysis, we identified four groups of DS-TB patients according to their levels of pro-inflammatory cytokines, angiogenic factors, and degree of lung damage. This study establishes that there is a correlation between VEGF-A and PF4 with platelets and classical monocytes during active TB, suggesting that those cell subpopulations are the major contributors of these molecules, and together, they control the severity of lung damage by amplification of the inflammatory environment.

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Section: Introductionmentioning

confidence: 99%

High levels of PF4, VEGF-A, and classical monocytes correlate with the platelets count and inflammation during active tuberculosis

et al. 2022

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“…In addition to these clinical programs a large number of nonclinical CCR1 antagonists have been described in both the published and in the patent literature, and since these have been extensively reviewed in a number of publications the reader is directed to these for an overall summary of ongoing progress in the CCR1 field (Pease and Horuk 2009;Zhang et al 2013).…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Cabp

2018

Encyclopedia of Signaling Molecules

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“…Enantiopure β-amino alcohols are frequently encountered in natural products and synthetic molecules 1 which display diverse bioactivities and excellent potential for pharmaceutical use ( Scheme 1a ). 2 In addition, these units are frequently used as chiral auxiliaries and ligands in asymmetric synthesis.…”

Section: Introductionmentioning

confidence: 99%