CD34 and CD43 Inhibit Mast Cell Adhesion and Are Required for Optimal Mast Cell Reconstitution

The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Immunity (Impact Factor: 21.56). 02/2005; 22(1):43-57. DOI: 10.1016/j.immuni.2004.11.014
Source: PubMed


CD34 is a cell-surface sialomucin expressed by hematopoietic stem cells (HSC), mast cells, and vascular endothelia. Despite its popularity as an HSC marker, the function of CD34 on hematopoietic cells remains enigmatic. Here, we have addressed this issue by examining the behavior of mutant mast cells lacking CD34, the related sialomucin, CD43, or both molecules. Loss of these molecules leads to a gene-dose-dependent increase in mast cell homotypic aggregation with CD34/CD43KOs > CD43KO > CD34KO > wild-type. Importantly, reexpression of CD34 or CD43 in these cells caused reversal of this phenotype. Furthermore, we find that loss of these sialomucins prevents mast cell repopulation and hematopoietic precursor reconstitution in vivo. Our data provide clear-cut evidence for a hematopoietic function for CD34 and suggest that it acts as a negative regulator of cell adhesion.

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Available from: Kelly M Mcnagny, Dec 13, 2013
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    • "The exact role of the sialomucins CD34 and CD43 in lymphocyte trafficking is unclear. CD34 deficiency results in heightened resistance to a variety of inflammatory diseases due to defects in migration of many cell types including mast cells [31], dendritic cells [20], [32] and granulocytes [23], [33]. CD43 has been shown to regulate TH cell migration to lymph nodes [24]. "
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    PLoS ONE 03/2013; 8(3):e60124. DOI:10.1371/journal.pone.0060124 · 3.23 Impact Factor
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    • "CD34 plays a key role in mast cell migration and development of allergic asthma [16,17], so we hypothesized that Cd34−/− mice would also be protected from PIA. However, following challenge, Cd34−/− mice exhibited equivalent decreases in body temperature (Figure 2A), clinical scores (Figure 2B) and serum histamine levels (Figure 2C) to wildtype control mice. "
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    ABSTRACT: Background Allergy to peanuts results in severe anaphylactic responses in affected individuals, and has dramatic effects on society and public policy. Despite the health impacts of peanut-induced anaphylaxis (PIA), relatively little is known about immune mechanisms underlying the disease. Using a mouse model of PIA, we evaluated mice with deletions in four distinct immune molecules (IL7Rα, L-selectin, CD34, CD103), for perturbed responses. Methods PIA was induced by intragastric sensitization with peanut antigen and cholera toxin adjuvant, followed by intraperitoneal challenge with crude peanut extract (CPE). Disease outcome was assessed by monitoring body temperature, clinical symptoms, and serum histamine levels. Resistant mice were evaluated for total and antigen specific serum IgE, as well as susceptibility to passive systemic anaphylaxis. Results PIA responses were dramatically reduced in IL7Rα−/− and L-selectin−/− mice, despite normal peanut-specific IgE production and susceptibility to passive systemic anaphylaxis. In contrast, CD34−/− and CD103−/− mice exhibited robust PIA responses, indistinguishable from wild type controls. Conclusions Loss of L-selectin or IL7Rα function is sufficient to impair PIA, while CD34 or CD103 ablation has no effect on disease severity. More broadly, our findings suggest that future food allergy interventions should focus on disrupting sensitization to food allergens and limiting antigen-specific late-phase responses. Conversely, therapies targeting immune cell migration following antigen challenge are unlikely to have significant benefits, particularly considering the rapid kinetics of PIA.
    Allergy Asthma and Clinical Immunology 08/2012; 8(1). DOI:10.1186/1710-1492-8-15 · 2.03 Impact Factor
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    • "On hematopoietic cells, we demonstrated a role for CD34 in facilitating mast cell and eosinophil migration. Mast cells derived from Cd34−/− bone marrow exhibited increased homotypic adhesion and impaired trafficking in vivo, compared to Cd34+/+ control cells [6], [12]. Cd34−/− animals also exhibited reduced tissue eosinophil recruitment in asthma and ulcerative colitis models and Cd34−/− eosinophils demonstrated a cell-intrinsic reduction in chemotaxis in vitro [6], [7]. "
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    ABSTRACT: Tumor growth and metastasis are determined by the complex interplay of factors, including those intrinsic to tumor cells and extrinsic factors associated with the tumor microenvironment. Our previous work demonstrated key roles for CD34 in the maintenance of vascular integrity and eosinophil and mast cell homing. Since both of these functions affect tumor development, we characterized the effect of CD34 ablation on tumor growth using the B16F1 melanoma model. Intriguingly, we found that CD34 plays a biphasic role in tumor progression. In early growth, both subcutaneous-injected tumors and intravenous-injected lung metastases grew more slowly in Cd34(-/-) mice. This correlated with abnormal vessel morphology and increased vascular permeability in these mice. Bone marrow transplantation experiments confirmed that this reflects a non-hematopoietic function of CD34. At later stages, subcutaneous tumor growth was accelerated in Cd34(-/-) mice and surpassed growth in wildtype mice. Bone marrow chimera experiments demonstrated this difference was due to a hematopoietic function for CD34 and, correspondingly we found reduced intra-tumor mast cell numbers in Cd34(-/-) mice. In aggregate, our analysis reveals a novel role for CD34 in both early and late tumor growth and provides novel insights into the role of the tumor microenvironment in tumor progression.
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