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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    • "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.
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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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