Search results for "platelets"
showing 10 items of 218 documents
Comparative study on biological effects of the guinea pig complement-peptide C3a and C3a-related synthetic oligopeptides
1980
Dose-response experiments with guinea pig C3a and a synthetic hexapeptide (amino acid residues 72–77), representing the COOH-terminal sequence of human C3a, were performed in two recently described bioassay systems for C3a, i.e. cytotoxicity against tumor cells measured as LDH and 51Cr-release and non cytolytic serotonin release from guinea pig platelets. Compared to the classical anaphylatoxic assay (guinea pig ileum contraction), nearly identical reactivities were observed in all three test systems with C3a and, although quantitatively different, with hexapeptide.
Differences in non-MHC restricted cytotoxic activities of human peripheral blood lymphocytes after transfusion with allogeneic leukocytes or platelet…
1990
Abstract MHC-unrestricted cytotoxic activity of peripheral blood lymphocytes (PBL) from 4–6 healthy donors was investigated before and after transfusion with allogeneic leukocytes or platelets. Natural killer and lectin-dependent cellular cytotoxicity (LDCC) of PBL was tested against K562 and Raji target cells in a 4-h and 16-h 51 Cr-release assay, respectively. After allotransfusion with leukocytes, we found increased cytotoxic activity of each donor's PBL against all the three targets on day 3 or 7. The highest non-specific cytotoxic activity was detected against the relatively NK resistant Raji target cells. The increase of cytotoxic activity was lowest against the LDCC target (PHA-treat…
Haemostasis in chronic kidney disease
2013
The coagulation system has gained much interest again as new anticoagulatory substances have been introduced into clinical practice. Especially patients with renal failure are likely candidates for such a therapy as they often experience significant comorbidity including cardiovascular diseases that require anticoagulation. Patients with renal failure on new anticoagulants have experienced excessive bleeding which can be related to a changed pharmacokinetic profile of the compounds. However, the coagulation system itself, even without any interference with coagulation modifying drugs, is already profoundly changed during renal failure. Coagulation disorders with either episodes of severe bl…
Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling p…
2014
One of the most important physiological platelet inhibitors is endothelium-derived prostacyclin which stimulates the platelet cyclic adenosine monophosphate/protein kinase A (cAMP/PKA)-signaling cascade and inhibits virtually all platelet-activating key mechanisms. Using quantitative mass spectrometry, we analyzed time-resolved phosphorylation patterns in human platelets after treatment with iloprost, a stable prostacyclin analog, for 0, 10, 30, and 60 seconds to characterize key mediators of platelet inhibition and activation in 3 independent biological replicates. We quantified over 2700 different phosphorylated peptides of which 360 were significantly regulated upon stimulation. This com…
The evolving role of platelets in inflammation.
2003
Platelets are small in size and simple in structure. Nevertheless, these anucleate cytoplasts utilize complex molecular systems to regulate a variety of biological functions. Here we review evolutionary paths, traditional roles, and previously unrecognized biological capacities of platelets that interface thrombosis with inflammation and potentially identify new roles in inflammatory diseases.
Novel α2β1 integrin inhibitors reveal that integrin binding to collagen under shear stress conditions does not require receptor preactivation.
2012
The interaction between α2β1 integrin (GPIa/IIa, VLA-2) and vascular collagen is one of the initiating events in thrombus formation. Here, we describe two structurally similar sulfonamide derivatives, BTT-3033 and BTT-3034, and show that, under static conditions, they have an almost identical effect on α2-expressing CHO cell adhesion to collagen I, but only BTT-3033 blocks platelet attachment under flow (90 dynes/cm(2)). Differential scanning fluorimetry showed that both molecules bind to the α2I domain of the recombinant α2 subunit. To further study integrin binding mechanism(s) of the two sulfonamides, we created an α2 Y285F mutant containing a substitution near the metal ion-dependent ad…
Potential and limitations of PKA/ PKG inhibitors for platelet studies
2021
Cyclic nucleotides (cAMP and cGMP) and corresponding protein kinases, protein kinase A (PKA) and protein kinase G (PKG), are the main intracellular mediators of endothelium-derived platelet inhibitors. Pharmacological PKA/PKG inhibitors are often used to discriminate between these two kinase activities and to analyze their underlying mechanisms. Previously we showed that all widely used PKG inhibitors (KT5823, DT3, RP isomers) either did not inhibit PKG or inhibited and even activated platelets independently from PKG. In this study, we examined several PKA inhibitors as well as inhibitors of adenylate and guanylate cyclases to reveal their effects on platelets and establish whether they are…
Effects of marine 2-polyprenyl-1,4-hydroquinones on phospholipase A2 activity and some inflammatory responses.
1995
Three 2-polyprenyl-1,4-hydroquinone derivatives (2-heptaprenyl-1,4-hydroquinone: IS1, 2-octaprenyl-1,4-hydroquinone: IS2 and 2-[24-hydroxy]-octaprenyl-1,4-hydroquinone: IS3) isolated from the Mediterranean sponge Ircinia spinosula, were evaluated for effects on phospholipase A2 activity of different origin (Naja naja venom, human recombinant synovial fluid and bee venom), as well as on human neutrophil function and mouse ear oedema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). IS1 interacted minimally with these responses. In contrast, IS2 and IS3 inhibited human recombinant synovial phospholipase A2 in a concentration-dependent manner, with minor effects on the rest of the enzymes…
Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity.
2001
One of the best known bioactive triterpenoids is oleanolic acid, a widespread 3-hydroxy-17-carboxy oleanane-type compound. In order to determine whether further oxidation of carbon 3 affects anti-inflammatory activity in mice, different tests were carried out on oleanolic acid and its 3-oxo-analogue oleanonic acid, which was obtained from Pistacia terebinthus galls. The last one showed activity on the ear oedema induced by 12-deoxyphorbol-13-phenylacetate (DPP), the dermatitis induced by multiple applications of 12-O-tetradecanoyl-13-acetate (TPA) and the paw oedemas induced by bradykinin and phospholipase A2. The production of leukotriene B4 from rat peritoneal leukocytes was reduced by ol…
TREM-1 ligand expression on platelets enhances neutrophil activation
2007
Abstract The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important role in the innate immune response related to severe infections and sepsis. Modulation of TREM-1–associated activation improves the outcome in rodent models for pneumonia and sepsis. However, the identity and occurrence of the natural TREM-1 ligands are so far unknown, impairing the further understanding of the biology of this receptor. Here, we report the presence of a ligand for TREM-1 on human platelets. Using a recombinant TREM-1 fusion protein, we demonstrate specific binding of TREM-1 to platelets. TREM-1–specific signals are required for the platelet-induced augmentation of polymorphonuclear leu…