title: Absence of platelet endothelial cell adhesion molecule-1 (CD31) leads to increased severity of local and systemic IgE-mediated anaphylaxis and modulation of mast cell activation.
abstract: Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a newly assigned member of the Ig-immunoreceptor tyrosine-based inhibitory motif superfamily, and its functional role is suggested to be an inhibitory receptor that modulates immunoreceptor tyrosine-based activation motif-dependent signaling cascades. In this study, we hypothesized that PECAM-1 plays an essential in vivo role as a counterregulator of immediate hypersensitivity reactions. We found that PECAM-1 was highly expressed on the surface of immature bone marrow mast cells and at a lower density on mature peritoneal mast cells. Examination of skin biopsies from PECAM-1(+/+) and PECAM-1(-/-) mice revealed that absence of PECAM-1 did not affect mast cell development or the capacity of mast cells to populate tissues. To examine whether the absence of PECAM-1 would influence immediate hypersensitivity reactions, PECAM-1(+/+) and PECAM-1(-/-) mice were presensitized with anti-DNP mouse IgE and then challenged 20 h later with DNP-BSA or PBS. PECAM-1(-/-) mice exhibited elevated serum histamine concentrations after Ag stimulation compared with PECAM-1(+/+) mice, indicating an increased severity of systemic IgE-mediated anaphylaxis. PECAM-1(-/-) mice have increased sensitivity to local cutaneous IgE-dependent anaphylaxis compared with PECAM-1(+/+) mice, as assessed by greater tissue swelling of their ears and mast cell degranulation in situ. PECAM-1(-/-) bone marrow mast cells showed enhanced dense granule serotonin release after Fc epsilon RI cross-linking in vitro. These results suggest that PECAM-1 acts as a counterregulator in allergic disease susceptibility and severity and negatively modulates mast cell activation.
authors.affiliation: Division of Hematology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia.
authors.forename: Mae-Xhum
authors.initials: MX
authors.lastname: Wong
authors.forename: Donna
authors.initials: D
authors.lastname: Roberts
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bartley
authors.forename: Denise E
authors.initials: DE
authors.lastname: Jackson
mesh_terms: D000707:Anaphylaxis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004198:Disease Susceptibility; D004487:Edema / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000378:metabolism / Q000502:physiology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000235:genetics / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics* / Q000502:physiology; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017455:Receptors, IgE; D007073:Immunoglobulin E