scholarly journals Changes in Activation States of Murine Polymorphonuclear Leukocytes (PMN) during Inflammation: a Comparison of Bone Marrow and Peritoneal Exudate PMN

2006 ◽  
Vol 13 (5) ◽  
pp. 575-583 ◽  
Author(s):  
Takuya Itou ◽  
L. Vincent Collins ◽  
Fredrik B. Thorén ◽  
Claes Dahlgren ◽  
Anna Karlsson
Keyword(s):  
Bone Marrow ◽  
Polymorphonuclear Leukocytes ◽  
Peritoneal Exudate ◽  
Ros Generation ◽  
Murine Models ◽  
Tnf Α ◽  
Chemotactic Peptides ◽  
Primed State ◽  
Factor Α ◽  
Necrosis Factor

ABSTRACT To study different activation states in polymorphonuclear leukocytes (PMN) in mice, we compared the function of murine PMN obtained from the bone marrow (BMPMN) with those of PMN obtained by intraperitoneal induction with thioglycolate (TGPMN) or uric acid (UAPMN). When stimulated with chemotactic peptides, e.g., formyl-methionyl-leucyl-phenylalanine (fMLF), WKYMVM, or WKYMVm, the TGPMN and UAPMN showed greatly enhanced generation of reactive oxygen species (ROS) compared with BMPMN, which suggests that exudation to the peritoneum per se induces a primed state in the cells. The WKYMVm peptide was the most potent stimulant of ROS generation, and it desensitized for subsequent stimulation with fMLF or WKYMVM. This desensitization was broken by the addition of cytochalasin B. The TGPMN and UAPMN appeared to be fully primed, since no increase in response was induced by pretreatment with tumor necrosis factor α (TNF-α). In contrast, the BMPMN response was increased 2.5- to 3-fold. The differences in oxidative responses were supported by degranulation studies. Preincubation with TNF-α promoted CR3 expression on BMPMN, and this level of expression was also enhanced by WKYMVm. In contrast, CR3 expression on untreated TGPMN and UAPMN was already similar to that on TNF-α-primed BMPMN and could be only slightly enhanced by TNF-α treatment. Taken together, these results indicate that BMPMN are in a resting state and have the capacity to become primed, while peritoneal exudate PMN are already fully primed upon isolation. These results have major implications for murine neutrophil research and show the importance of defining which PMN subsets to use when investigating murine models.

scholarly journals Effect of soluble interleukin-6 receptor α and interleukin-6 secreted by polymorphonuclear leukocytes on tumor necrosis factor-α expression and its production by peripheral blood mononuclear cells

2002 ◽  
Vol 11 (5) ◽  
pp. 325-328 ◽  
Author(s):  
E. Jablonska
Keyword(s):  
Interleukin 6 ◽  
Polymorphonuclear Leukocytes ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Interleukin 6 Receptor ◽  
Factor Α ◽  
Necrosis Factor

Background: It has recently been shown that soluble interleukin-6 receptor (sIL-6R) alone or complexed with interleukin (IL)-6, besides their regulatory role in a wide variety of both normal and abnormal biologic reactions mediated by IL-6, could be an effective stimulator of the cell function.Aims: The key question of the present study is whether the sIL-6Rα or sIL-6R with IL-6 released by polymorphonuclear leukocytes (PMN) can influence cytokine secretion such as tumor necrosis factor-α (TNF-α) by peripheral blood mononuclear cells (PBMC), which together with PMN develop the inflammatory and immune response of a host.Methods: Cells were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 1 h at 37°C in 5% CO2. After incubation, the culture supernatant of PMN was removed and was added to PBMC. The PBMC were cultured for 1 h at 37°C in the same conditions. In the culture supernatants and lysates of PMN, we examined the concentrations of sIL-6R by enzyme-linked immunosorbent assay (ELISA). TNF-α was measured at both protein and mRNA levels. Protein levels were determined by ELISA. To examine TNF-α mRNA expression, we isolated mRNA from PBMC after culture, using TRIZOL Reagent. The quantity of mRNA TNF-α was determined by the Quantikine mRNA assay.Results and conclusion: The results obtained revealed that sIL-6R with IL-6 secreted by PMN may play a regulatory role in the immune response by modulating the TNF-α expression and its production by PBMC. This may have a significant influence on an early phase of the inflammation and other reactions mediated by TNF-α.

scholarly journals Tumor Necrosis Factor α Stimulates Osteoclast Differentiation by a Mechanism Independent of the Odf/Rankl–Rank Interaction

2000 ◽  
Vol 191 (2) ◽  
pp. 275-286 ◽  
Author(s):  
Kanichiro Kobayashi ◽  
Naoyuki Takahashi ◽  
Eijiro Jimi ◽  
Nobuyuki Udagawa ◽  
Masamichi Takami ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Fab Fragment ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) stimulates the differentiation of osteoclast progenitors of the monocyte/macrophage lineage into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF, also called CSF-1). When mouse bone marrow cells were cultured with M-CSF, M-CSF–dependent bone marrow macrophages (M-BMMφ) appeared within 3 d. Tartrate-resistant acid phosphatase–positive osteoclasts were also formed when M-BMMφ were further cultured for 3 d with mouse tumor necrosis factor α (TNF-α) in the presence of M-CSF. Osteoclast formation induced by TNF-α was inhibited by the addition of respective antibodies against TNF receptor 1 (TNFR1) or TNFR2, but not by osteoclastogenesis inhibitory factor (OCIF, also called OPG, a decoy receptor of ODF/RANKL), nor the Fab fragment of anti–RANK (ODF/RANKL receptor) antibody. Experiments using M-BMMφ prepared from TNFR1- or TNFR2-deficient mice showed that both TNFR1- and TNFR2-induced signals were important for osteoclast formation induced by TNF-α. Osteoclasts induced by TNF-α formed resorption pits on dentine slices only in the presence of IL-1α. These results demonstrate that TNF-α stimulates osteoclast differentiation in the presence of M-CSF through a mechanism independent of the ODF/RANKL–RANK system. TNF-α together with IL-1α may play an important role in bone resorption of inflammatory bone diseases.

scholarly journals Analysis of Bone Marrow-derived Mesenchymal Stem Cell Kinetics after Short-term Stimulation with Tumor Necrosis Factor-α (TNF-α)

2019 ◽  
Vol 28 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Mio Naritani ◽  
Miho Inoue ◽  
Resmi Raju ◽  
Mayu Miyagi ◽  
Masamitsu Oshima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Cell Kinetics ◽  
Short Term ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti–tumor necrosis factor-α antibody therapy

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 474-482 ◽  
Author(s):  
Helen A. Papadaki ◽  
Heraklis D. Kritikos ◽  
Vasilis Valatas ◽  
Dimitrios T. Boumpas ◽  
George D. Eliopoulos
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
Chronic Disease ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Anemia Of Chronic Disease ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Circumstantial evidence has implicated tumor necrosis factor α (TNF-α) in the pathogenesis of anemia of chronic disease (ACD) in rheumatoid arthritis (RA). We investigated the role of TNF-α in erythropoiesis of patients with active RA (n = 40) and the effect of anti–TNF-α antibody administration (cA2). Patients with RA had lower numbers of CD34+/CD71+ and CD36−/glycophorin A+ (glycoA+) bone marrow (BM) cells and increased proportions of apoptotic cells within the CD34+/CD71+ and CD36+/glycoA+ cell compartments, compared to healthy controls (n = 24). Erythroid burst-forming units (BFU-Es) obtained by BM mononuclear or purified CD34+ cells were significantly lower in RA patients compared to controls. These abnormalities were more pronounced among patients with ACD. Increased TNF-α levels in patient long-term BM culture supernatants inversely correlated with BFU-Es and hemoglobin levels and positively with the percentage of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells. Following cA2 therapy, a normalization was documented in the number of CD34+/CD71+ and CD36−/glycoA+ cells, the number of BFU-Es, and the proportion of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells, which was associated with a significant increase in hemoglobin levels compared to baseline. Recovery from anemia was more prominent in patients with ACD. The exogenous addition of an anti–TNF-α antibody in the cultures increased BFU-E number in patients prior to cA2 treatment but not after treatment, further substantiating the inhibitory role of TNF-α on patients' erythropoiesis. We conclude that TNF-α–mediated apoptotic depletion of BM erythroid cells may account for ACD in RA and that cA2 administration may ameliorate ACD in these patients by down-regulating the apoptotic mechanisms involved in erythropoiesis.

The let-7f-5p–Nme4 pathway mediates tumor necrosis factor α-induced impairment in osteogenesis of bone marrow-derived mesenchymal stem cells

2021 ◽  
pp. 1-11
Author(s):  
Ying-Jie Zhao ◽  
Zheng-Chao Gao ◽  
Xi-Jing He ◽  
Jing Li
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tumor Necrosis Factor ◽  
Osteogenic Differentiation ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Although tumor necrosis factor α (TNF-α)-mediated inflammation significantly impacts osteoporosis, the mechanisms underlying the osteogenic differentiation defects of bone marrow-derived mesenchymal stem cells (BM-MSCs) caused by TNF-α remain poorly understood. We found that TNF-α stimulation of murine BM-MSCs significantly upregulated the expression levels of several microRNAs (miRNAs), including let-7f-5p, but this increase was significantly reversed by treatment with the kinase inhibitor BAY 11-7082. To study gain- or loss of function, we transfected cells with an miRNA inhibitor or miRNA mimic. We then demonstrated that let-7f-5p impaired osteogenic differentiation of BM-MSCs in the absence and presence of TNF-α, as evidenced by alkaline phosphatase and alizarin red staining as well as quantitative assays of the mRNA levels of bone formation marker genes in differentiated BM-MSCs. Moreover, let-7f-5p targets the 3′ untranslated region of Nucleoside diphosphate kinase 4 (Nme4) mRNA and negatively regulates Nme4 expression in mouse BM-MSCs. Ectopic expression of Nme4 completely reversed the inhibitory effects of the let-7f-5p mimic on osteogenic differentiation of mouse BM-MSCs. Furthermore, inhibition of let-7f-5p or overexpression of Nme4 in BM-MSCs restored in-vivo bone formation in an ovariectomized animal model. Collectively, our work indicates that let-7f-5p is involved in TNF-α-mediated reduction of BM-MSC osteogenesis via targeting Nme4.

Abstract 5551: Double Deficiency of Tumor Necrosis Factor-α and Interferon-γ in Bone Marrow-Derived Cells Prevents Neointimal Formation in a Murine Model of Vascular Injury

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideki Murayama ◽  
Masafumi Takahashi ◽  
Yuji Shiba ◽  
Masaya Takamoto ◽  
Hirohiko Ise ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vascular Injury ◽  
Tumor Necrosis ◽  
Interferon Γ ◽  
Neointimal Formation ◽  
Tnf Α ◽  
Bone Marrow Derived Cells ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Neointimal formation after percutaneous coronary intervention (PCI), termed restenosis, limits therapeutic revascularization. Recent evidence indicates that inflammatory responses induced by inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), are involved in the progression of neointimal formation. However, the role of TNF-α and IFN-γ in the restenosis after PCI has not been fully understood. The purpose of this study is to examine the impact of TNF-α and IFN-γ in bone marrow-derived cells in the development of neointimal formation after vascular injury in mice. Wild-type (WT), TNF-α-deficient (TNF-α −/− ), IFN-γ-deficient (IFN-γ −/− ), and TNF-α/IFN-γ double-deficient (DKO) mice were subjected to wire-mediated vascular injury of the right femoral artery. Immunohistochemical analysis showed the expression of TNF-α and IFN-γ was detected in the neointimal lesion of WT mice, but these cytokines were not detected in the lesion of the corresponding deficient mice. Neointimal formation was significantly reduced after the injury in the DKO mice, compared to that in the WT, TNF-α −/− , and IFN-γ −/− mice (I/M ratio, WT: 2.28±0.17, TNF-α −/− : 2.13±0.20, IFN-γ −/− : 2.37±0.16, DKO: 1.32±0.10, p<0.05, each n=14–17). No significant difference in reendothelialization (CD31 staining) was observed among these groups. Further, vascular smooth muscle cell (α-SMA) and macrophage (F4/80) contents in the neointimal area also did not differ among the groups. The number of proliferating cell nuclear antigen (PCNA) and Ki-67 positive cells in the neointimal lesion was significantly decreased in DKO mice. To determine the contribution of bone marrow cells, we developed 3 types of bone marrow chimeric (BMT Wild→Wild , BMT DKO→Wild , and BMT Wild→DKO ) mice. The neointimal formation in BMT DKO→Wild mice was significantly reduced as compared to that in BMT Wild→Wild (I/M ratio, p<0.05, each n=7) and BMT Wild→DKO mice (p<0.05). These results suggest that the lack of TNF-α and IFN-γ in bone marrow-derived cells synergistically prevents neointimal formation after vascular injury and provide new insights into the mechanisms underlying the restenosis after PCI.

An intrinsic thyrotropin-mediated pathway of TNF-α production by bone marrow cells

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Heuy-Ching Wang ◽  
Jolene Dragoo ◽  
Qin Zhou ◽  
John R. Klein
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Hematopoietic Cells ◽  
Thyroid Stimulating Hormone ◽  
Appreciable Change ◽  
Tnf Α ◽  
Factor Α ◽  
Inductive Signal ◽  
Necrosis Factor

Abstract Recent studies have identified a role for thyroid-stimulating hormone (TSH; ie, thyrotropin) as an inductive signal for tumor necrosis factor-α (TNF-α) secretion by bone marrow (BM) cells, although the features of that activation pathway have not been defined. Using intracellular TSH staining and enzyme-linked immunoassay for detection of secreted TSH, we demonstrate that TSH synthesis in BM cells occurs within CD45+ (leukocyte common antigen) hematopoietic cells and that the majority of that activity resides in a component of CD11b+ BM cells that are not mature T cells, B cells, or Thy-1+ cells in the BM. Conversely, TSH-responsive BM cells defined by expression of TSH receptor (TSHR) using flow cytometry were selectively associated with a nonerythroid CD11b− lymphocyte precursor population. In vitro culture of magnetic-activated cell sorted CD11b− and CD11b+ cells with titrated amounts of purified TSH resulted in significantly higher levels of TNF-α secretion from CD11b− BM cells compared to non-TSH–treated cells, with no appreciable change in TNF-α production from CD11b+cells. These findings are the first to demonstrate TSH production by BM hematopoietic cells, and they demonstrate that TSH may be involved in the regulation of TNF-α by CD11b− BM cells. They also indicate that TSH-mediated regulation of TNF-α secretion within the BM most likely operates through an intrinsic network of TSH production and use between different types of BM cells, and they suggest that local TSH may be an important homeostatic regulator of hematopoiesis mediated by TNF-α.

Endothelial permeability and IL-6 production during hypoxia: role of ROS in signal transduction

1999 ◽  
Vol 277 (5) ◽  
pp. L1057-L1065 ◽  
Author(s):  
Mir H. Ali ◽  
Scott A. Schlidt ◽  
Navdeep S. Chandel ◽  
Karen L. Hynes ◽  
Paul T. Schumacker ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Umbilical Vein ◽  
Endothelial Permeability ◽  
Ros Generation ◽  
Transendothelial Electrical Resistance ◽  
Tnf Α ◽  
Factor Α ◽  
Induced Changes ◽  
Necrosis Factor

Prolonged hypoxia produces reversible changes in endothelial permeability, but the mechanisms involved are not fully known. Previous studies have implicated reactive oxygen species (ROS) and cytokines in the regulation of permeability. We tested whether prolonged hypoxia alters permeability to increasing ROS generation, which amplifies cytokine production. Human umbilical vein endothelial cell (HUVEC) monolayers were exposed to hypoxia while secretion of tumor necrosis factor-α (TNF-α), interleukin (IL)-1α, IL-6, and IL-8 was measured. IL-6 and IL-8 secretion increased fourfold over 24 h in a pattern corresponding to changes in HUVEC permeability measured by transendothelial electrical resistance (TEER). Addition of exogenous IL-6 to normoxic HUVEC monolayers caused time-dependent changes in TEER that mimicked the hypoxic response. An antibody to IL-6 significantly attenuated the hypoxia-induced changes in TEER (86 ± 4 vs. 63 ± 3% with hypoxia alone at 18 h), whereas treatment with anti-IL-8 had no effect. To determine the role of hypoxia-induced ROS on this response, HUVEC monolayers were incubated with the antioxidants ebselen (50 μM) and N-acetyl-l-cysteine (NAC, 1 mM) before hypoxia. Antioxidants attenuated hypoxia-induced IL-6 secretion (13 ± 2 pg/ml with ebselen and 19 ± 3 pg/ml with NAC vs. 140 ± 15 pg/ml with hypoxia). Ebselen and NAC prevented changes in TEER during hypoxia (94 ± 2% with ebselen and 90 ± 6% with NAC vs. 63 ± 3% with hypoxia at 18 h). N-nitro-l-arginine (500 μM) did not decrease hypoxia-induced changes in dichlorofluorescin fluorescence, IL-6 secretion, or TEER. Thus ROS generated during hypoxia act as signaling elements, regulating secretion of the proinflammatory cytokines that lead to alterations of endothelial permeability.

Phagocytosis of Co-Developing Megakaryocytic Progenitors by Dendritic Cells in the Culture with Thrombopoietin and Tumor Necrosis Factor-α: Possible Role in Hemophagocytic Syndrome.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3082-3082
Author(s):  
Kenichi Sawada ◽  
Makoto Hirokawa ◽  
Kayo Inaba ◽  
Hiroshi Fukaya ◽  
Yoshinari Kawabata ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hemophagocytic Syndrome ◽  
Cytokine Production ◽  
Bone Marrow Cells ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Number Of Cells

Abstract Background. Tumor necrosis factor-α (TNF-α) and thrombopoietin (TPO) have been shown to sustain differentiation and proliferation of CD34+ cells toward dendritic cells (DCs) in the presence of multi-acting cytokines. We hypothesized that co-stimulation of TPO and TNF-α generate megakaryocytic progenitors and DCs together from human CD34+ cells and that interaction of these cells may provide a physiological and/or a pathological role of DCs in megakaryopoiesis. Materials and Methods. Highly purified human CD34+ cells were cultured with TPO, with or without TNF-α, in plasma-depleted medium and induced to undergo megakaryocytic differentiation. We enumerated megakaryocytic progenitor cells using the specific markers CD41, CD42b, and CD61, and DCs using CD4, CD11c, CD80, CD83, CD86, and CD123. The character and roles of co-developing non-megakaryocytic cells in the presence of TNF-α were analyzed by fluorescence-activated cell sorter, enzyme immunohistochemistry, confocal microscopy, and autologous mixed lymphocyte reaction. Cytokine production was assessed using a cytometric bead array system. Results. When CD34+ cells were cultured for 7 days in the presence of TPO, the generated cells predominantly expressed CD41 (95±2%), CD42b (54±12%), and CD61 (96±2%), while rarely expressing CD11c (1.6±1.3%), CD80 (0.1±0.1%), CD83 (0.8±0.6%), or CD86 (3.3±1.9%). The addition of TNF-α significantly decreased the number of cells expressing CD41 (3.0±0.6%), CD42b (3.3±1.0%), or CD61 (3.2±0.9%), but did not affect the number of total cells. In the presence of TNF-α, the generated cells expressed major histocompatibility complex (MHC) class I (100%) plus MHC class II (100%). A substantial number of cells became positive for CD11c (37±1%), and even co-stimulatory molecules such as CD80 (2.4±1.9%), CD83 (8±4%), and CD86 (18±7%). Immature CD11c+ DCs were physically associated with apoptotic and CD61+ cells and capable of endocytosing CD61+ cells. Most of the CD11c+ cells co-expressed the c-mpl TPO receptor, CD4, and CD123 and about one half of CD11c+ cells co-expressed CD86. The DCs generated by TNF-α and TPO, but not those by TNF-α alone, facilitated autologous T cell proliferation in some extent, although cytokine production from activated T cells were low. We also confirmed engulfment of CD61+ cells and their fragment by CD11c+ cells in bone marrow cells from patients with hemophagocytic syndromes. Conclusions. This is the first report showing that in the presence of TNF-α, the non-megakaryocytic cells with typical feature of DCs are co-generated from human CD34+ cells during megakaryocytic differentiation by TPO. The CD4+ CD11c+ CD123+ DCs physically associates with and phagocytose developing or dying immature megakaryocytic cells. Similar phenomenon showing engulfment of CD61+ fragment by CD11c+ cells was also observed in bone marrow cells from patients with hemophagocytic syndrome. Therefore, it may be conceivable that DCs with phagocytic activity during the development in bone marrow may play a crucial role in the maintenance of tolerance for self-substances derived from hematopoietic progenitor cells.

scholarly journals Platelet-Endothelial Interactions in Inflamed Mesenteric Venules

Blood ◽  
1998 ◽  
Vol 91 (4) ◽  
pp. 1318-1324 ◽  
Author(s):  
Paul S. Frenette ◽  
Caitlin Moyna ◽  
Daqing W. Hartwell ◽  
John B. Lowe ◽  
Richard O. Hynes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Wild Type ◽  
Membrane Glycoproteins ◽  
Active Function ◽  
Tnf Α ◽  
Thrombin Activation ◽  
Selectin Ligand ◽  
Factor Α ◽  
Necrosis Factor

Abstract The selectins are membrane glycoproteins promoting adhesive events between leukocytes, platelets, and endothelial cells. We have previously demonstrated that platelets roll on P-selectin expressed on stimulated endothelium. In this study, we wished to examine the function of both the platelet and endothelial selectins, P- and E-selectins, in mediating platelet-endothelial interactions during inflammation. We demonstrate, using intravital microscopic examination of venules inflamed with tumor necrosis factor-α (TNF-α), that resting platelets interact with both P- and E-selectins and that the leukocyte α(1,3)fucosyltransferases FucT IV and FucT VII do not provide platelets with selectin ligand activity. We also show that after thrombin activation of wild-type (+/+) platelets, platelet P-selectin can mediate interactions on a TNF-α–inducible endothelial ligand. To evaluate the potential role of platelet P-selectin in the recruitment of leukocytes to inflammatory sites, we reconstituted the bone marrow of mice deficient in both P- and E-selectins (P/E−/−) with wild-type (+/+) or P-selectin–deficient (P−/−) bone marrow containing megakaryocytic precursors. Providing +/+ platelets to P/E−/− mice by bone marrow transplantation did not rescue the immunodeficient phenotype, suggesting that platelet P-selectin does not have an active function in the recruitment of leukocytes into inflammatory sites. To participate in inflammatory or hemostatic responses, platelets may use the endothelial selectins.

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