Thrombocytopenia in Liver Transplant Recipients

Chang, Feng Yee; Singh, Nina; Gayowski, Timothy; Wagener, Marilyn M.; Mietzner, S.; Stout, Janet E.; Marino, Ignazio R.

doi:10.1097/00007890-200001150-00014

Cited by 105 publications

(30 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, thrombin stimulation increases platelet adherence to injured or infected vascular endothelial cells, promoting platelet accu- Although the physiologic relevance of thrombin-mediated HPAP release in host defense is not yet proven, several studies suggest that thrombin and platelets play a role in preventing and/or limiting infection. For example, thrombocytopenia has been shown to put experimental animals (37) and humans (5,38) at significantly increased risk of infection. Furthermore, thrombin participates in key cellular events that regulate inflammatory responses (28,40,47,48).…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Peptides from Human Platelets

Tang¹,

2002

View full text Add to dashboard Cite

Platelets share structural and functional similarities with granulocytes known to participate in antimicrobial host defense. To evaluate the potential antimicrobial activities of platelet proteins, normal human platelets were stimulated with human thrombin in vitro. Components of the stimulated-platelet supernatants were purified to homogeneity by reversed-phase high-performance liquid chromatography. Purified peptides with inhibitory activity against Escherichia coli ML35 in an agar diffusion antimicrobial assay were characterized by mass spectrometry, amino acid analysis, and sequence determination. These analyses enabled the identification of seven thrombin-releasable antimicrobial peptides from human platelets: platelet factor 4 (PF-4), RANTES, connective tissue activating peptide 3 (CTAP-3), platelet basic protein, thymosin ␤-4 (T␤-4), fibrinopeptide B (FP-B), and fibrinopeptide A (FP-A). With the exception of FP-A and FP-B, all peptides were also purified from acid extracts of nonstimulated platelets. The in vitro antimicrobial activities of the seven released peptides were further tested against bacteria (E. coli and Staphylococcus aureus) and fungi (Candida albicans and Cryptococcus neoformans). Each peptide exerted activity against at least two organisms. Generally, the peptides were more potent against bacteria than fungi, activity was greater at acidic pHs, and antimicrobial activities were dose dependent. Exceptions to these observations were observed with PF-4, which displayed a bimodal dose-response relationship in microbicidal assays, and T␤-4, which had greater activity at alkaline pHs. At concentrations at which they were individually sublethal, PF-4 and CTAP-3 exerted synergistic microbicidal activity against E. coli. Collectively, these findings suggest a direct antimicrobial role for platelets as they are activated to release peptides in response to trauma or mediators of inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Antimicrobial Peptides from Human Platelets

Tang¹,

2002

View full text Add to dashboard Cite

show abstract

“…For example, Sullam et al (33) observed that animals rendered selectively thrombocytopenic (but not neutropenic) have significantly worse infective endocarditis due to a PMPsusceptible strain of viridans group streptococci than animals with normal platelet counts. Human studies have also shown thrombocytopenia to be an independent risk factor for infection in organ transplant patients and other patient populations (5,12,35). To our knowledge, no prospective studies have specifically addressed potential relationships between platelet antagonism and an increased risk of infection due to S. aureus.…”

Section: Fig 4 Effects Of Platelet Surface Adhesin Antagonists On Amentioning

confidence: 99%

Platelet Antistaphylococcal Responses Occur through P2X ₁ and P2Y ₁₂ Receptor-Induced Activation and Kinocidin Release

et al. 2008

View full text Add to dashboard Cite

Platelets (PLTs) act in antimicrobial host defense by releasing PLT microbicidal proteins (PMPs) or PLT kinocidins (PKs). Receptors mediating staphylocidal efficacy and PMP or PK release versus isogenic PMP-susceptible (ISP479C) and -resistant (ISP479R) Staphylococcus aureus strains were examined in vitro. Isolated PLTs were incubated with ISP479C or ISP479R (PLT/S. aureus ratio range, 1:1 to 10,000:1) in the presence or absence of a panel of PLT inhibitors, including P2X and P2Y receptor antagonists of increasingly narrow specificity, and PLT adhesion receptors (CD41, CD42b, and CD62P). PLT-to-S. aureus exposure ratios of >10:1 yielded significant reductions in the viability of both strains. Results from reversed-phase high-performance liquid chromatography indicated that staphylocidal PLT releasates contained PMPs and PKs. At ratios below 10:1, the PLT antistaphylococcal efficacy relative to the intrinsic S. aureus PMP-susceptible or -resistant phenotype diminished. Apyrase (an agent of ADP degradation), suramin (a general P2 receptor antagonist), pyridoxal 5-phosphonucleotide derivative (a specific P2X 1 antagonist), and cangrelor (a specific P2Y 12 antagonist) mitigated the PLT staphylocidal response against both strains, correlating with reduced levels of PMP and PK release. Specific inhibition occurred in the presence and absence of homologous plasma. The antagonism of the thromboxane A 2 , cyclooxygenase-1/ cyclooxygenase-2, or phospholipase C pathway or the hindrance of surface adhesion receptors failed to impede PLT anti-S. aureus responses. These results suggest a multifactorial PLT anti-S. aureus response mechanism involving (i) a PLT-to-S. aureus ratio sufficient for activation; (ii) the ensuing degranulation of PMPs, PKs, ADP, and/or ATP; (iii) the activation of P2X 1 /P2Y 12 receptors on adjacent PLTs; and (iv) the recursive amplification of PMP and PK release from these PLTs.

show abstract

“…In this connection, it is interesting that important risk groups for invasive aspergillosis, e.g., patients with chemotherapy-induced neutropenia and recipients of hematopoietic stem cell transplants (6,13), very often have concurrent thrombocytopenia in addition to neutropenia. Furthermore, it has been reported that liver transplant recipients with thrombocytopenia have a considerably higher incidence of fungal infection than nonthrombocytopenic patients (3). There are some reports on the interaction between A. fumigatus and platelets, showing inhibition of fungal growth potentially involving the release of known plateletderived microbial peptides, as well as direct physical interaction between platelets and conidia or hyphae (4,16).…”

mentioning

confidence: 99%

Activation of Platelets byAspergillus fumigatusand Potential Role of Platelets in the Immunopathogenesis of Aspergillosis

Rødland

Ueland

Pedersen³

et al. 2010

Infect Immun

View full text Add to dashboard Cite

Aspergillus fumigatus is the most frequent cause of invasive mold infections worldwide. Platelets contribute to inflammation and promote thrombosis, characteristically seen in aspergillosis, and might be involved both in antifungal defense and in the histopathological process. In the experiments reported here, in vitro activation of platelets by conidia, swollen conidia, and hyphae from A. fumigatus was assessed by flow cytometry and enzyme immunoassays. THP-1 monocytes and human monocytes with and without platelets were cultured with hyphae from A. fumigatus, and the release of interleukin-8 (IL-8) was measured by enzyme immunoassays. A. fumigatus potently induced the expression of CD62-p and CD63 and the release of CD40 ligand, RANTES, and Dickkopf homolog 1 in platelets, with particularly enhancing effects of hyphae compared with conidia. The hypha-mediated activation of platelets further enhanced the release of IL-8 both in THP-1 monocytes and in human adherent monocytes. In conclusion, we have found that A. fumigatus is a potent inducer of platelet-mediated inflammation, potentially promoting protective as well as harmful responses during aspergillosis.Aspergillosis is the most common mold infection worldwide, and Aspergillus fumigatus accounts for more than 90% of the cases (6). In contrast to most human pathogens, which are encountered infrequently, A. fumigatus spores are inhaled on a daily basis, and occasionally, exposure to large numbers of conidia can occur. The first-line host defense against Aspergillus infection is based on innate immunity mediated by monocytes/macrophages and neutrophils (11,12,17,18). The adaptive immune system responds to a pathogen only after it has been recognized by the innate immune system (11). While inadequate immune responses may predispose to invasive disease, overly robust responses can result in immune-mediated inflammatory tissue damage. Thus, imbalanced immune responses to A. fumigatus may result in a spectrum of human disease states ranging from allergic bronchopulmonary aspergillosis to invasive aspergillosis in the immunocompromised host (9). Despite better diagnostic tools and therapeutic advances, the infection is difficult to diagnose and treat, and the outcome of invasive aspergillosis is often fatal.Several lines of evidence support a role for platelets in inflammation (10). Platelet-mediated inflammation has been demonstrated during various acute and chronic infections, and it has been suggested that platelets contribute to antimicrobial defenses (5, 8). Very little is known about the role of platelets in defense against Aspergillus infection. In this connection, it is interesting that important risk groups for invasive aspergillosis, e.g., patients with chemotherapy-induced neutropenia and recipients of hematopoietic stem cell transplants (6, 13), very often have concurrent thrombocytopenia in addition to neutropenia. Furthermore, it has been reported that liver transplant recipients with thrombocytopenia have a considerably higher incidence of fungal infe...

show abstract

Thrombocytopenia in Liver Transplant Recipients

Cited by 105 publications

References 20 publications

Antimicrobial Peptides from Human Platelets

Antimicrobial Peptides from Human Platelets

Platelet Antistaphylococcal Responses Occur through P2X ₁ and P2Y ₁₂ Receptor-Induced Activation and Kinocidin Release

Activation of Platelets byAspergillus fumigatusand Potential Role of Platelets in the Immunopathogenesis of Aspergillosis

Contact Info

Product

Resources

About

Thrombocytopenia in Liver Transplant Recipients

Cited by 105 publications

References 20 publications

Antimicrobial Peptides from Human Platelets

Antimicrobial Peptides from Human Platelets

Platelet Antistaphylococcal Responses Occur through P2X 1 and P2Y 12 Receptor-Induced Activation and Kinocidin Release

Activation of Platelets byAspergillus fumigatusand Potential Role of Platelets in the Immunopathogenesis of Aspergillosis

Contact Info

Product

Resources

About

Platelet Antistaphylococcal Responses Occur through P2X ₁ and P2Y ₁₂ Receptor-Induced Activation and Kinocidin Release