Prothrombotic roles of substance-P, neurokinin-1 receptors and leukocytes in the platelet-dependent clot formation in whole blood

Azma, Toshiharu; Matsubara, Yuki; Kinoshita, Hiroyuki; Hidaka, Ikuhiro; Shiraishi, Seiji; Nakao, Masakazu; Kawamoto, Masashi; Yuge, Osafumi; Hatano, Yoshio

doi:10.1007/s11239-008-0215-0

Cited by 7 publications

(3 citation statements)

References 26 publications

(39 reference statements)

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“…A number of different types of non-neuronal cells including lymphocytes and monocytes possess SP and its specific NK1-R(Marriotte et al, 2001); however, the pathophysiological roles of SP in these cells remain to be established SP promotes platelet-dependent clot formation through NK1-R, in which leukocytes are involved (Azma et al, 2009). SP triggers functional responses in many cells of the immune system through NK1-R including inflammatory processes and immunologic responses, involving monocytes, macrophages, lymphocytes, microglia, natural killer cells, and precursors of immune cells (Douglas et al, 2011; Lai et al, 1998; Ho et al, 2002; Ho et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Substance P–Neurokinin-1 receptor interaction upregulates monocyte tissue factor

Khan

Douglas

Benton

2012

Journal of Neuroimmunology

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Monocytes play an important role in hemostasis. In this study, the prothrombotic effects of the neuropeptide substance P (SP) on human monocytes through neurokinin-1 receptor (NK1-R) were characterized. SP upregulated monocyte tissue factor (TF), the major coagulation cascade stimulator, in a concentration and time dependent manner. Specific inhibition of NK1-R completely blocked TF expression. Monocytes stimulated by SP released cytokines and chemokines. When monocytes were stimulated with cytokines or chemokines, TF was expressed by the cytokines (GM-CSF, IFN-γ and TNF-α). Cytokines may play a major role in the mechanism of SP induced monocyte TF expression. NK1-R antagonists (NK1-RA) may have a role in developing novel therapeutic approaches to patients vulnerable to vaso-occlusive disorders.

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Section: Discussionmentioning

confidence: 99%

Substance P–Neurokinin-1 receptor interaction upregulates monocyte tissue factor

Khan

Douglas

Benton

2012

Journal of Neuroimmunology

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“…C5a activation of mast cells stimulates production of plasminogen activator inhibitor (PAI)-1 and antagonizes t-PA production (Wojta et al, 2002), suggesting that additional mast cell activators, such as thrombin (Theoharides et al, 2011) and SP (Hermans et al, 2018), may have similar effects. SP also induces monocyte tissue factor expression (Khan et al, 2012) and promotes platelet clot formation (Azma et al, 2009). Understanding SP binding interactions with NK1 (Johnson et al, 2016) and Mas-related receptors (Green et al, 2019) on monocytes, mast cells and platelets may therefore be important hemostatic regulators in COVID-19 patients.…”

Section: Sars-cov-2 and Coagulationmentioning

confidence: 99%

COVID-19 Usurps Host Regulatory Networks

2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the cell surface and this complex is internalized. ACE2 serves as an endogenous inhibitor of inflammatory signals associated with four major regulator systems: the renin-angiotensin-aldosterone system (RAAS), the complement system, the coagulation cascade, and the kallikrein-kinin system (KKS). Understanding the pathophysiological effects of SARS-CoV-2 on these pathways is needed, particularly given the current lack of proven, effective treatments. The vasoconstrictive, prothrombotic and pro-inflammatory conditions induced by SARS-CoV-2 can be ascribed, at least in part, to the activation of these intersecting physiological networks. Moreover, patients with immune deficiencies, hypertension, diabetes, coronary heart disease, and kidney disease often have altered activation of these pathways, either due to underlying disease or to medications, and may be more susceptible to SARS-CoV-2 infection. Certain characteristic COVID-associated skin, sensory, and central nervous system manifestations may also be linked to viral activation of the RAAS, complement, coagulation, and KKS pathways. Pharmacological interventions that target molecules along these pathways may be useful in mitigating symptoms and preventing organ or tissue damage. While effective anti-viral therapies are critically needed, further study of these pathways may identify effective adjunctive treatments and patients most likely to benefit.

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“…The concentration of this drug was required to inhibit the function of NK1R in vivo as previously described. 12…”

Section: Inhibition Study By Neurokinin Receptor Antagonistmentioning

confidence: 99%

Involvement of L-Selectin in Contact Hypersensitivity Responses Augmented by Auditory Stress

Bae

Shimizu

Yozaki

et al. 2010

The American Journal of Pathology

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Stress affects the pathophysiology of cutaneous immune reactions, including contact hypersensitivity (CH) in individuals sensitized with sensitizing hapten, where local endothelial cell activation plays a critical role. To clarify the effects of stress in cutaneous immune reactions, we selected a CH model using annoying sound as a stress. Furthermore, we conducted the stress experiments by using selectin-deficient mice to determine the involvement of selectin molecules regarding local endothelial activation. Auditory stress augmented CH responses in the present study. Namely, ear thickness and mast cell numbers were significantly increased in stressed CH mice. mRNA expression of preprotachykinin-A, a precursor of substance-P; interferon-gamma; interleukin (IL)-4; IL-6; and tumor necrosis factor-alpha significantly increased in stressed CH mice. Furthermore, stressed L-selectin-deficient mice showed significant decreases in all parameters mentioned above relative to stressed wild-type mice in CH response. Meanwhile, treatment with anti-L-selectin Ab resulted in a significant decrease in ear thickness and mRNA levels of interferon-gamma, IL-4, IL-6, and tumor necrosis factor-alpha, but failed to significantly reduce preprotachykinin-A mRNA levels and mast cell numbers. Our results indicated that auditory stress enhances CH response and that the augmentation of this CH response might be mediated through L-selectin, but not through P- or E-selectin pathways.

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Prothrombotic roles of substance-P, neurokinin-1 receptors and leukocytes in the platelet-dependent clot formation in whole blood

Cited by 7 publications

References 26 publications

Substance P–Neurokinin-1 receptor interaction upregulates monocyte tissue factor

Substance P–Neurokinin-1 receptor interaction upregulates monocyte tissue factor

COVID-19 Usurps Host Regulatory Networks

Involvement of L-Selectin in Contact Hypersensitivity Responses Augmented by Auditory Stress

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