Cell surface proteoglycan expression during maturation of human monocytes-derived dendritic cells and macrophages

Wegrowski, Yanusz; Milard, A.-L.; Kotlarz, Grazyna; Toulmonde, E.; Maquart, François‐Xavier; Bernard, Jacky

doi:10.1111/j.1365-2249.2006.03059.x

Cited by 61 publications

(58 citation statements)

References 55 publications

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“…Monocytes, unlike platelets, also express GAG side chains composed of dermatan sulfate (DS) and heparan sulfate (HS) as well, 24,25 both of which bind PF4 with higher affinity than CS, 1 making the bound PF4 more resistant to elution by heparin. Moreover, monocytes express hypersulfated GAGs when induced to differentiate to macrophages, which may further enhance PF4 binding.…”

Section: Introductionmentioning

confidence: 99%

Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia

Rauova

Hirsch

Greene

et al. 2010

Blood

144

160

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Heparin-induced thrombocytopenia (HIT)is a life-and limb-threatening thrombotic disorder that develops after exposure to heparin, often in the setting of inflammation. We have shown previously that HIT is associated with antibodies to complexes that form between platelet factor 4 and glycosaminoglycan (GAG) side chains on the surface of platelets. However, thrombosis can occur in the absence of thrombocytopenia. We now show that platelet factor 4 binds to monocytes and forms antigenic complexes with their surface GAG side chains more efficiently than on platelets likely due to differences in GAG composition. Binding to monocytes is enhanced when the cells are activated by endotoxin. Monocyte accumulation within developing arteriolar thrombi was visualized by situ microscopy. Monocyte depletion or inactivation in vivo attenuates thrombus formation induced by photochemical injury of the carotid artery in a modified murine model of HIT while paradoxically exacerbating thrombocytopenia. These studies demonstrate a previously unappreciated role for monocytes in the pathogenesis of arterial thrombosis in HIT and suggest that therapies targeting these cells might provide an alternative approach to help limit thrombosis in this and possibly other thrombotic disorders that occur in the setting of inflammation. IntroductionPlatelet factor 4 (PF4) is a cationic chemokine with high affinity for unfractionated heparin (UFH) and other large, negatively charged molecules. 1 PF4 is stored in platelet ␣-granules, released upon activation, when it then binds rapidly to glycosaminoglycan (GAG) side chains expressed on the surface of platelets 2 and other vascular cells, with little remaining free in the circulation. 3 Heparin-induced thrombocytopenia (HIT) is an iatrogenic complication of heparin therapy caused by antibodies that recognize complexes of human (h) PF4 with heparin or other GAGs. 4,5 In solution, formation of antigenic complexes between PF4 and heparin is critically dependent on their molar ratio, with loss of antibody binding when the optimal ratio is disrupted by an excess of either component. 6,7 Antigen formation on the platelet surface also follows a bell-shaped curve as PF4 concentration is increased, with maximal binding of antibody seen at an exogenous PF4 concentration of 50 g/mL. 8 Chondroitin sulfates (CSs) are the predominant GAG side chains expressed on platelets. 9,10 We have shown that the binding of the HIT-like monoclonal antibody KKO 11 to platelets is abrogated by chondroitinase ABC, 8 indicating that HIT antibodies bind to PF4/CS complexes on this cell type. Therapeutic concentrations of UFH disrupt antibody binding in part by eluting PF4 from the platelet surface, which reduces formation of antigenic complexes and the potential for platelet activation 8 through platelet Fc␥RIIA. 12 Thus, variation in the expression of platelet-derived PF4 (or CS) might help to explain why only a small percentage of patients who generate antibodies to PF4/UFH develop HIT. 13 Although it has been generally accepte...

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Section: Introductionmentioning

confidence: 99%

Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia

Rauova

Hirsch

Greene

et al. 2010

Blood

144

160

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“…Therefore, since our data imply a minimal presence of core proteins in Jurkat cells causing poor bacterial attachment, the gene expression of PG-core proteins was assessed using RT-PCR analysis. Syndecan-1, syndecan-2, syndecan-4, betaglycan, glypican-1, and thrombomodulin are expressed in epithelial and endothelial cells [38,39], and CD44 is expressed in lymphocytes [39,40].…”

Section: Discussionmentioning

confidence: 99%

“…Reportedly, the major PG of lymphocytes is the CD44 molecule, which is expressed on the cell surface and is a component of GAGs such as chondroitin sulfate [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

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Chlamydophila pneumoniae attachment and infection in low proteoglycan expressing human lymphoid Jurkat cells

Kobayashi

Ishida

Matsuo

et al. 2011

Microbial Pathogenesis

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This study investigated the proteoglycan (PG)-dependent mechanism ofImmunofluorescent co-staining with antibodies against chlamydial LPS and heparin did not identify bacterial and heparin co-localization on Jurkat cells. We also confirmed that when C. pneumoniae was statically infected to human CD4 + peripheral blood lymphocytes known not expressing detectable level of heparin, the bacteria attached to and formed inclusion bodies in the cells. Thus, the attachment mechanism of C.pneumoniae to Jurkat cells with low PG expression is unique when compared withHEp-2 cells and potentially independent of GAGs such as heparin.

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“…Interestingly, some of up-regulated genes were associated with the maturation process of DCs. These include TNF-α (a maturation-inducing cytokine), Sdc-1 (a cell surface proteoglycan induced during the maturation process), Map2k4 (a member of MAP kinase kinase family associated with migration and maturation of DC) and Socs2 (a suppressor of cytokine signaling molecule induced during the maturation process) [12,19,40]. In addition, up-regulation was also detected on defensin and cathelin, which were formerly considered to work just as antimicrobial peptides [6,8] and recently reported to have cell migration activity and to be associated with DC maturation process [25].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Changes Induced by Type IV Allergy-Inducible Chemicals in Dendritic Cells

Tarama

Kato

Ishikawa

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. In the present study, the changes of gene expression profile in dendritic cell (DC)-derived DC2.4 cells sensitized with two allergenic chemicals were analyzed by microarray analysis to develop a basis for an in vitro assessment system of type IV allergenic chemicals. Consequently, 26 genes were significantly up-regulated, and 53 were down-regulated in both groups. Interestingly, some of upregulated genes were associated with the maturation process of DCs. A set of genes was further evaluated by real-time reverse transcription-polymerase chain reaction to identify the gene expression changes specifically induced by type IV allergy-inducible chemicals in DC2.4 cells, and 2 possible candidates, syndecan-1 (Sdc1) and smoothened (SMO) genes were identified. Thus, up-regulation of Sdc1 gene and down-regulation of SMO gene in DC2.4 cells may be diagnostic markers for the screening of type IV-allergenic chemicals. KEY WORDS: chemical, dendritic cell, microarray analysis, type IV allergy.J. Vet. Med. Sci. 70 (7): [673][674][675][676][677][678][679][680] 2008 Allergic contact dermatitis (ACD), a type IV allergy, is one of the most common inflammatory diseases of the skin with unknown genetic basis and is often an occupationally related disorder in industrialized countries with an important socio-medical impact [14,28]. At present, many chemicals are considered to have allergenic potency and thus risk assessment of such chemical substances is important. ACD has been intensively studied, and the development of an allergic hypersensitivity reaction in the skin is considered to be processes depending on the induction of specific T-lymphocyte responses [23]. At the initial step, chemical allergens exposed on the skin are recognized by Langerhans cells (LCs), the principal DC residing in the epidermis and known to play a key role in the development of ACD. Following an encounter with a chemical allergen, LCs are activated and subsequently migrate from the skin to the draining lymph nodes, undergoing a maturation process during the journey [20,22].For many years, guinea pigs have been applied for the hazard analysis of skin-sensitizing chemicals [9,26]. Recently, the local lymph node assay (LLNA) was developed in mice as an alternative approach based on the characterization of initial proliferative responses in draining lymph nodes caused by chemicals exposure [16,21,34,39], and this method is now widely used for estimation of the allergenic potency of chemical substances. Although these approaches are sensitive and reliable, more advantageous ways in terms of cost performance, safety, readiness and animal welfare are expected. More recently, in vitro assay for chemical substances with allergenic potency is extensively explored by using cultured cells, especially macrophages [5,41]. In these experiments, up-regulation of several molecules including cell surface markers were reported to be induced by chemical exposure, suggesting that these markers may be candidates for evaluating chemicals with allergenic potency [5...

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Cell surface proteoglycan expression during maturation of human monocytes-derived dendritic cells and macrophages

Cited by 61 publications

References 55 publications

Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia

Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia

Chlamydophila pneumoniae attachment and infection in low proteoglycan expressing human lymphoid Jurkat cells

Gene Expression Changes Induced by Type IV Allergy-Inducible Chemicals in Dendritic Cells

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