Internalization of IgG-Coated Targets Results in Activation and Secretion of Soluble CD40 Ligand and RANTES by Human Platelets

Antczak, Adam; Vieth, Joshua A.; Singh, Navinderjit; Worth, Randall G.

doi:10.1128/cvi.00296-10

Cited by 32 publications

(33 citation statements)

References 44 publications

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“…RANTES is stored in platelet a-granule and recruits inflammatory cells to sites of infection. 31,32 It was newly discovered that platelets are a source of MIF, a cytokine with chemokine-like features. 1,29,30 We recently showed that RANTES is secreted from platelets over time upon stimulation in suspension with the oral pathogen P. gingivalis and Pam 3 CSK 4 , showing that the chemokine is secreted from platelets as an immune response.…”

Section: Discussionmentioning

confidence: 99%

Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation

et al. 2014

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Platelets are considered to have important functions in inflammatory processes as key players in innate immunity. Toll like receptors (TLRs), expressed on platelets, recognize pathogen associated molecular patterns and trigger immune responses. Pathogens are able to adhere to human tissues and form biofilms which cause a continuous activation of the immune system. The authors aimed to investigate how immobilized Pam3CSK4 (a synthetic TLR2/1 agonist) and IgG, respectively, resembling a bacterial focus, affects adhesion and activation of platelets including release of two cytokines, regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). The authors also aim to clarify the signaling downstream of TLR2/1 and FcγRII (IgG receptor) and the role of adenine nucleotides in this process. Biolayers of Pam3CSK4 and IgG, respectively, were confirmed by null-ellipsometry and contact angle measurements. Platelets were preincubated with signaling inhibitors for scr and Syk and antagonists for P2X1 or P2Y1 [adenosine triphosphate (ATP), adenosine diphosphate (ADP) receptors] prior to addition to the surfaces. The authors show that platelets adhere and spread on both Pam3CSK4- and IgG-coated surfaces and that this process is antagonized by scr and Syc inhibitors as well as P2X1 and P2Y antagonists. This suggests that Pam3CSK4 activated platelets utilize the same pathway as FcγRII. Moreover, the authors show that ATP-ligation of P2X1 is of importance for further platelet activation after TLR2/1-activation, and that P2Y12 is the prominent ADP-receptor involved in adhesion and spreading. RANTES and MIF were secreted over time from platelets adhering to the coated surfaces, but no MIF was released upon stimulation with soluble Pam3CSK4. These results clarify the importance of TLR2/1 and FcγRII in platelet adhesion and activation, and strengthen the role of platelets as an active player in sensing bacterial infections.

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Section: Discussionmentioning

confidence: 99%

Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation

et al. 2014

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“…These interactions require various platelet surface proteins, including toll‐like receptors, fibrinogen receptors, and FcγRIIA (Fitzgerald et al ., ; Blair et al ., ). FcγRIIA is the only IgG receptor present on human platelet surfaces and is responsible for binding and internalization of IgG‐containing targets (King et al ., ; Worth et al ., ; Antczak et al ., ). Specifically, we have recently shown that platelets are capable of binding and internalizing IgG‐coated latex beads, and the internalization is dependent on FcγRIIA and actin polymerization, similar to phagocytosis observed in leukocytes (Antczak et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Human platelets efficiently kill IgG-opsonizedE. coli

Riaz

Tasma

Woodman

et al. 2012

FEMS Immunol Med Microbiol

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Platelets are known contributors of hemostasis but have recently been shown to be important in inflammation and infectious diseases. Moreover, thrombocytopenia is often observed in patients with sepsis. We previously reported that platelets actively phagocytosed IgG-coated latex beads. In the current study, the capacity of human platelets to participate in host defense against bacterial infections was determined by assessing their ability to kill E. coli. Washed human platelets were incubated with unopsonized or IgG-opsonized E. coli and evaluated for binding and killing of E. coli. We found that although both unopsonized and IgG-opsonized E. coli associated with platelets, only IgG-opsonized E. coli were efficiently killed unless platelets were activated by a potent agonist. The bactericidal activity was dependent on FcγRIIA, was sensitive to cytochalasin D, but was not due to reactive oxygen metabolites. These data suggest that platelets may play an important role in protection against infection.

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“…For instance, CCL5 can be expressed by platelets, endothelial cells, bronchial epithelial cells, and cells of the immune system (e.g. macrophages, monocytes, natural killer cells, and dendritic cells) [8]. Kruppel-like factor 13 (KLF13) controls the transcription of CCL5 in T lymphocytes [9].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Discovering the Role of CCL5 in Metastatic Breast Cancer

Khalid¹,

Wolfram²,

Ferrari³

et al. 2015

MRMC

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The most common cause of mortality in cancer patients is metastasis. Therefore, a variety of therapeutic strategies are currently under investigation to develop effective drugs that can target and inhibit factors that promote tumor invasion. Considerable emphasis has been placed on studying cancer as an inflammatory process that proceeds in a dynamic microenvironment. In fact, the tumor microenvironment has been implicated to contribute considerably to metastasis. For instance, chemokine C-C motif ligand 5 (CCL5) produced by cells in the tumor microenvironment has been established as an important contributor to metastatic disease. Recently, the role of CCL5 in breast cancer invasion has been extensively studied. This review summarizes the recent developments in regards to this chemokine, including the conditions that increase the generation of CCL5 and the effects mediated by this signaling pathway. Moreover, the potential use of CCL5 and its receptor chemokine C-C motif receptor 5 (CCR5) as a target for treating and/or preventing breast cancer metastasis is also discussed.

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Internalization of IgG-Coated Targets Results in Activation and Secretion of Soluble CD40 Ligand and RANTES by Human Platelets

Cited by 32 publications

References 44 publications

Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation

Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation

Human platelets efficiently kill IgG-opsonizedE. coli

Recent Advances in Discovering the Role of CCL5 in Metastatic Breast Cancer

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