Quantitation of surface CD14 on human monocytes and neutrophils

Antal‐Szalmás, Péter; Strijp, Jos A. G. van; Weersink, A. J. L.; Verhoef, J.; Kessel, Kok P. M. van

doi:10.1002/jlb.61.6.721

Cited by 141 publications

(138 citation statements)

References 46 publications

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“…It should be noted that hESC-derived neutrophils showed a high level of CD14 expression ( Figure 4A). In general, CD14 is considered a marker of monocytes in peripheral blood, although it is well known that CD14 is also expressed on granulocytes, but at a much lower level (14,15). Our data indicate that both granulocytic and monocytic cells generated in vitro express a high level of CD14 and analysis of CD14 expression should not be used for discrimination of monocytic lineage from granulocytic in in vitro differentiation cultures.…”

Section: Figurementioning

confidence: 74%

Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell–derived lin–CD34+CD43+CD45+ progenitors

Choi¹,

Vodyanik²,

Slukvin³

2009

J. Clin. Invest.

193

199

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Basic research into human mature myelomonocytic cell function, myeloid lineage diversification and leukemic transformation, and assessment of myelotoxicity in preclinical drug development requires a constant supply of donor blood or bone marrow samples and laborious purification of mature myeloid cells or progenitors, which are present in very small quantities. To overcome these limitations, we have developed a protocol for efficient generation of neutrophils, eosinophils, macrophages, osteoclasts, DCs, and Langerhans cells from human embryonic stem cells (hESCs). As a first step, we generated lin -CD34 + CD43 + CD45 + hematopoietic cells highly enriched in myeloid progenitors through coculture of hESCs with OP9 feeder cells. After expansion in the presence of GM-CSF, these cells were directly differentiated with specific cytokine combinations toward mature cells of particular types. Morphologic, phenotypic, molecular, and functional analyses revealed that hESC-derived myelomonocytic cells were comparable to their corresponding somatic counterparts. In addition, we demonstrated that a similar protocol could be used to generate myelomonocytic cells from induced pluripotent stem cells (iPSCs). This technology offers an opportunity to generate large numbers of patient-specific myelomonocytic cells for in vitro studies of human disease mechanisms as well as for drug screening.

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Section: Figurementioning

confidence: 74%

Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell–derived lin–CD34+CD43+CD45+ progenitors

Choi¹,

Vodyanik²,

Slukvin³

2009

J. Clin. Invest.

193

199

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“…3A). Because the mechanism of action of 15C1 in neutralizing LPS signaling is supposed to involve the direct recognition of TLR4 through its Ag-combining sites and the contemporary engagement of CD32A through its Fc portion (48), we tested the effect of IV.3 mAb, which specifically recognizes CD32A (55). However, as shown in Fig.…”

Section: Binding To Tlr4 By Stx Triggers the Release Of Cxcl8 By Neutmentioning

confidence: 99%

Identification of TLR4 as the Receptor That Recognizes Shiga Toxins in Human Neutrophils

Brigotti

Carnicelli

Arfilli

et al. 2013

The Journal of Immunology

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Hemolytic uremic syndrome (HUS) caused by intestinal Shiga toxin–producing Escherichia coli infections is a worldwide health problem, as dramatically exemplified by the German outbreak occurred in summer 2011 and by a constant burden of cases in children. Shiga toxins (Stx) play a pivotal role in HUS by triggering endothelial damage in kidney and brain through globotriaosylceramide (Gb3Cer) receptor targeting. Moreover, Stx interact with human neutrophils, as experimentally demonstrated in vitro and as observed in patients with HUS. A neutrophil-protective role on endothelial damage (sequestration of circulating toxins) and a causative role in toxin delivery from the gut to the kidney (piggyback transport) have been suggested in different studies. However, the receptor that recognizes Stx in human neutrophils, which do not express Gb3Cer, has not been identified. In this study, by competition and functional experiments with appropriate agonists and antagonists (LPS, anti-TLR4 Abs, respectively), we have identified TLR4 as the receptor that specifically recognizes Stx1 and Stx2 in human neutrophils. Accordingly, these treatments displaced both toxin variants from neutrophils and, upon challenge with Stx1 or Stx2, neutrophils displayed the same pattern of cytokine expression as in response to LPS (assessed by quantitative RT-PCR, ELISA, or multiplexed Luminex-based immunoassays). Moreover, data were supported by adequate controls excluding any potential interference of contaminating LPS in Stx-binding and activation of neutrophils. The identification of the Stx-receptor on neutrophils provides additional elements to foster the understanding of the pathophysiology of HUS and could have an important effect on the development of therapeutic strategies.

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“…This receptor is present at high density on the cell membrane (mCD14) of monocytes and macrophages, and at low density on polymorphonuclear leukocytes. It is also found as a soluble protein (sCD14) in human serum and urine (Antal-Szalmas et al, 1997 ;Ulevitch & Tobias, 1994). CD14 lacks transmembrane and cytokine-binding domains and is not believed to have intrinsic signalling capabilities.…”

Section: Introductionmentioning

confidence: 99%

Porins from Salmonella enterica serovar Typhimurium induce TNF-α, IL-6 and IL-8 release by CD14-independent and CD11a/CD18-dependent mechanisms

et al. 2001

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Quantitation of surface CD14 on human monocytes and neutrophils

Abstract: Abstract:The absolute number of membrane-

Cited by 141 publications

References 46 publications

Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell–derived lin–CD34+CD43+CD45+ progenitors

Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell–derived lin–CD34+CD43+CD45+ progenitors

Identification of TLR4 as the Receptor That Recognizes Shiga Toxins in Human Neutrophils

Porins from Salmonella enterica serovar Typhimurium induce TNF-α, IL-6 and IL-8 release by CD14-independent and CD11a/CD18-dependent mechanisms

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