Effect of human defensins on the cytoplasmic Ca2+ content in platelets

Ткаченко, С. Б.; Kokryakov, V. N.; Ашмарин, И. П.; Грачев, С. В.; Кубатиев, Аслан Амирханович

doi:10.1007/bf02445732

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…When washing off the PMN secretion we could not observe a significant change in phagocytosis, suggesting direct activation of macrophages by components of the PMN secretion rather than an opsonization of the bacteria to be responsible for the enhanced phagocytosis. This is supported further by measurements of intracellular Ca 2+ , which resemble a similar pattern, as activation in response to HBP [7,17], cathepsin G [18] and defensins [19] is similar to the macrophage activation by PMN secretion found in this study. Therefore, this group of PMN‐derived polypeptides and other PMN proteins are probable candidates in the effect described here.…”

Section: Discussionsupporting

confidence: 88%

Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages

Soehnlein

Kenne

Rotzius

et al. 2007

Clinical and Experimental Immunology

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SummaryMacrophages represent a multi-functional cell type in innate immunity that contributes to bacterial clearance by recognition, phagocytosis and killing. In acute inflammation, infiltrating neutrophils release a wide array of preformed granule proteins which interfere functionally with their environment. Here, we present a novel role for neutrophil-derived granule proteins in the antimicrobial activity of macrophages. Neutrophil secretion obtained by antibody cross-linking of the integrin subunit CD18 (X-link secretion) or by treatment with N-Formyl-Met-Leu-Phe (fMLP secretion) induced a several-fold increase in bacterial phagocytosis by monocytes and macrophages. This response was associated with a rapid activation of the monocytes and macrophages as depicted by an increase in cytosolic free Ca 2+ . Interestingly, fMLP secretion had a more pronounced effect on monocytes than the X-link secretion, while the opposite was observed for macrophages. In addition, polymorphonuclear cells (PMN) secretion caused a strong enhancement of intracellular reactive oxygen species (ROS) formation compared to incubation with bacteria. Thus, secretion of neutrophil granule proteins activates macrophages to increase the phagocytosis of bacteria and to enhance intracellular ROS formation, indicating pronounced intracellular bacterial killing. Both mechanisms attribute novel microbicidal properties to PMN granule proteins, suggesting their potential use in anti-microbial therapy.

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Section: Discussionsupporting

confidence: 88%

Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages

Soehnlein

Kenne

Rotzius

et al. 2007

Clinical and Experimental Immunology

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“…Our observation that HNPs induce platelet activation is in disagreement with conclusions made in previous studies. The group of Kubtiev reported that HNPs inhibit agonist‐induced platelet aggregation as well as agonist‐induced increase of platelet cytoplasmatic Ca 2+ levels [57,58]. However, in both studies an HNP‐enriched extract from human blood was used, whereas we used pure synthetic HNP‐1.…”

Section: Discussionmentioning

confidence: 99%

Human neutrophil alpha‐defensins induce formation of fibrinogen and thrombospondin‐1 amyloid‐like structures and activate platelets via glycoprotein IIb/IIIa

Horn

Bertling

Brodde

et al. 2012

Journal of Thrombosis and Haemostasis

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Summary. Background: Human neutrophil α‐defensins (HNPs) are important constituents of the innate immune system. Beyond their antimicrobial properties, HNPs also have pro‐inflammatory features. While HNPs in plasma from healthy individuals are barely detectable, their level is strongly elevated in septic plasma and plasma from patients with acute coronary syndromes. Objectives: As thrombosis and inflammation are intertwined processes and activation of human polymorphonuclear leukocytes (PMNL) and subsequent degranulation is associated with full activation of surrounding platelets, we studied the effect of HNPs on platelet function. Methods: The effect of HNPs on platelet activation parameters and apoptosis was investigated via aggregometry, flow cytometry, confocal microscopy and the ELISA technique. Results: It was found that HNPs activate platelets in pathophysiologically relevant doses, inducing fibrinogen and thrombospondin‐1 binding, aggregation, granule secretion, sCD40L shedding, and procoagulant activity. HNPs bound directly to the platelet membrane, induced membrane pore formation, microparticle formation, mitochondrial membrane depolarization and caspase‐3‐activity. Confocal microscopy revealed the HNP‐induced formation of polymeric fibrinogen and thrombospondin‐1 amyloid‐like structures, which bound microorganisms. Platelets adhered to these structures and formed aggregates. Blocking of glycoprotein IIb/IIIa (GPIIb/IIIa) markedly inhibited HNP‐induced platelet activation. In addition, heparin, heparinoid, serpins and α2‐macroglobulin, which all bind to HNPs, blocked HNP‐1‐induced platelet activation in contrast to direct thrombin inhibitors such as hirudin. Conclusions: HNPs activate platelets and induce platelet apoptosis by formation of amyloid‐like proteins. As these structures entrapped bacteria and fungi, they might reflect an additional function of HNPs in host defense. The described mechanism links again thrombosis and infection.

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“…The most widely described mechanism of action of antimicrobial peptides is the induction of membrane permeabilization through the formation of multimeric pores (28). Antimicrobial peptides can be cytotoxic at high concentrations (27), but specific peptides, at lower concentrations, have been shown to possess mitogenic, chemotactic or cytokine modulatory activities (29, 30), as well as acting to inhibit protein kinase C (31) and stimulate Ca ++ mobilization (32), signaling mechanisms of relevance to cold ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

Successful Six‐Day Kidney Preservation Using Trophic Factor Supplemented Media and Simple Cold Storage

McAnulty

Reid

Waller

et al. 2002

American Journal of Transplantation

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This study examined the effect of trophic factor supplementation [TFS; bovine neutrophil peptide-1 (bactenecin), 1 mg/L; substance P, 2.5 mg/L; nerve growth factor, 20 mg/L; epidermal growth factor, 10 mg/L; insulin-like growth factor-1, 10 mg/L] during cold storage with UW lactobionate solution. Dogs transplanted with kidneys stored for 4 days in TFS-UW had significantly lower peak serum creatinine values (mean 2.9 ∫ 0.2 mg/dL) and returned to normal values faster (6 days) than kidneys stored for 3 days in unmodified UW solution (4.2 ∫ 0.3 mg/dL and 14 days, respectively). Kidneys stored for 5 days in TFS-UW (mean peak creatinine 3.7 ∫ 0.3) functioned equivalently to kidneys stored for 3 days and better than kidneys stored for 4 days in UW alone. Dogs with kidneys stored for 6 days in TFS-UW had mean peak creatinines of 5.7 ∫ 0.4 mg/dL. These returned to normal creatinine values in 14 days, equal to 3-day stored and significantly better than kidneys stored for 4 days in UW alone (20 days recovery time). This study shows trophic factor deprivation appears to be a critical mechanism of injury in organ preservation with current synthetic storage media, and marks the initial development of a synthetic biologically active preservation solution, the next generation of preservation media.

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Effect of human defensins on the cytoplasmic Ca2+ content in platelets

Cited by 3 publications

References 12 publications

Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages

Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages

Human neutrophil alpha‐defensins induce formation of fibrinogen and thrombospondin‐1 amyloid‐like structures and activate platelets via glycoprotein IIb/IIIa

Successful Six‐Day Kidney Preservation Using Trophic Factor Supplemented Media and Simple Cold Storage

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