Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3

Shah, Sajeel A.; Kanabar, Varsha; Riffo‐Vasquez, Yanira; Mohamed, Zainab; Cleary, Simon J.; Corrigan, Christopher; Elliot, John; Shute, Janis K.; Page, Clive; Pitchford, Simon

doi:10.1165/rcmb.2020-0425oc

Cited by 20 publications

(35 citation statements)

References 63 publications

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“…Indeed, a recent study showed that CCR3 (CCL11 receptor) is essential for the recruitment of platelets into asthmatic lungs in the models of allergic inflammation. Under intravital microscopy, the rolling, adhesion, and extravascular migration of platelets in the HDM-sensitized murine models were markedly suppressed by SB328437, a CCR3 antagonist [36]. A study on platelet degranulation function in hemostasis and inflammation revealed that AHR and eosinophilic inflammation were significantly diminished in platelet-specific Munc13-4 KO mice, as the dense granule release was abrogated in these mice [45].…”

Section: Rantes Release↑mentioning

confidence: 99%

Platelets, Not an Insignificant Player in Development of Allergic Asthma

Luo

Zhang

Lee

et al. 2021

Cells

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Allergic asthma is a chronic and heterogeneous pulmonary disease in which platelets can be activated in an IgE-mediated pathway and migrate to the airways via CCR3-dependent mechanism. Activated platelets secrete IL-33, Dkk-1, and 5-HT or overexpress CD40L on the cell surfaces to induce Type 2 immune response or interact with TSLP-stimulated myeloid DCs through the RANK-RANKL-dependent manner to tune the sensitization stage of allergic asthma. Additionally, platelets can mediate leukocyte infiltration into the lungs through P-selectin-mediated interaction with PSGL-1 and upregulate integrin expression in activated leukocytes. Platelets release myl9/12 protein to recruit CD4+CD69+ T cells to the inflammatory sites. Bronchoactive mediators, enzymes, and ROS released by platelets also contribute to the pathogenesis of allergic asthma. GM-CSF from platelets inhibits the eosinophil apoptosis, thus enhancing the chronic inflammatory response and tissue damage. Functional alterations in the mitochondria of platelets in allergic asthmatic lungs further confirm the role of platelets in the inflammation response. Given the extensive roles of platelets in allergic asthma, antiplatelet drugs have been tested in some allergic asthma patients. Therefore, elucidating the role of platelets in the pathogenesis of allergic asthma will provide us with new insights and lead to novel approaches in the treatment of this disease.

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Section: Rantes Release↑mentioning

confidence: 99%

Platelets, Not an Insignificant Player in Development of Allergic Asthma

Luo

Zhang

Lee

et al. 2021

Cells

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“…Therefore, we decided to use the CCR3 antagonist SB328437 to determine whether the blockade of this receptor would also be a beneficial pain treatment. A few animal studies examining SB328437 as an experimental agent for treatment have been conducted in renal cell carcinoma ( 62 ), allergic inflammation ( 63 ) or osteoarthritis models ( 64 ); however, SB328437 treatment of neuropathic pain has not been assessed. In a chronic constriction injury model of the sciatic nerve, we observed for the first time that the aforementioned antagonist reduced pain-like behavior after repeated i.t.…”

Section: Discussionmentioning

confidence: 99%

Blockade of CC Chemokine Receptor Type 3 Diminishes Pain and Enhances Opioid Analgesic Potency in a Model of Neuropathic Pain

et al. 2021

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Neuropathic pain is a serious clinical issue, and its treatment remains a challenge in contemporary medicine. Thus, dynamic development in the area of animal and clinical studies has been observed. The mechanisms of neuropathic pain are still not fully understood; therefore, studies investigating these mechanisms are extremely important. However, much evidence indicates that changes in the activation and infiltration of immune cells cause the release of pronociceptive cytokines and contribute to neuropathic pain development and maintenance. Moreover, these changes are associated with low efficacy of opioids used to treat neuropathy. To date, the role of CC chemokine receptor type 3 (CCR3) in nociception has not been studied. Similarly, little is known about its endogenous ligands (C-C motif ligand; CCL), namely, CCL5, CCL7, CCL11, CCL24, CCL26, and CCL28. Our research showed that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with upregulation of CCL7 and CCL11 in the spinal cord and dorsal root ganglia (DRG). Moreover, our results provide the first evidence that single and repeated intrathecal administration of the CCR3 antagonist SB328437 diminishes mechanical and thermal hypersensitivity. Additionally, repeated administration enhances the analgesic properties of morphine and buprenorphine following nerve injury. Simultaneously, the injection of SB328437 reduces the protein levels of some pronociceptive cytokines, such as IL-6, CCL7, and CCL11, in parallel with a reduction in the activation and influx of GFAP-, CD4- and MPO-positive cells in the spinal cord and/or DRG. Moreover, we have shown for the first time that an inhibitor of myeloperoxidase-4-aminobenzoic hydrazide may relieve pain and simultaneously enhance morphine and buprenorphine efficacy. The obtained results indicate the important role of CCR3 and its modulation in neuropathic pain treatment and suggest that it represents an interesting target for future investigations.

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“…Conversely, platelets, through other secreted mediators, may participate to tissue repair and inflammatory response resolution. So far, to our knowledge, no study has investigated the exact role of platelets in lung tissue and its significance in asthma pathology [127]. In OVA-sensitised and challenged mice, circulating platelet-leukocyte complexes are increased, and platelet-associated leukocytes exhibit elevated expression of the adhesion molecule CD11b [54].…”

Section: Platelets In Asthma and Other Chronic Respiratory Diseasesmentioning

confidence: 99%

Platelets: a potential role in chronic respiratory diseases?

et al. 2021

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Platelets are small anucleate cells known for their role in haemostasis and thrombosis. In recent years, an increasing number of observations have suggested that platelets are also immune cells and key modulators of immunity. They express different receptors and molecules that allow them to respond to pathogens, and to interact with other immune cells. Platelets were linked to the pathogenesis of some inflammatory disorders including respiratory diseases such as asthma and idiopathic pulmonary fibrosis. Here, we discuss the involvement of platelets in different immune responses, and we focus on their potential role in various chronic lung diseases.

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Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3

Cited by 20 publications

References 63 publications

Platelets, Not an Insignificant Player in Development of Allergic Asthma

Platelets, Not an Insignificant Player in Development of Allergic Asthma

Blockade of CC Chemokine Receptor Type 3 Diminishes Pain and Enhances Opioid Analgesic Potency in a Model of Neuropathic Pain

Platelets: a potential role in chronic respiratory diseases?

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