title: Requirement for CD45 in fine-tuning mast cell responses mediated by different ligand-receptor systems.
abstract: The receptor-like protein tyrosine phosphatase CD45, the most abundant cell surface phosphatase on all nucleated hemopoietic cells, is a critical regulator of the activation status of Src family kinases (SFKs). To study the impact of CD45 on mast cell function, we compare bone marrow-derived mast cells (BMMCs) from CD45-deficient mice and from mice expressing an activating point mutation (E613R) in the juxtamembrane wedge of CD45. In response to Ag-triggered FcepsilonR1-mediated activation, CD45-deficient BMMCs exhibit increased inhibitory Lyn phosphorylation and drastically reduced effector functions (degranulation and cytokine secretion). In contrast, CD45 E613R BMMCs show stronger effector functions after Ag-triggering than wild-type (WT) BMMCs. Despite these dichotomous phenotypes, phosphorylation of the inhibitory tyrosine in the SFK Lyn of CD45 E613R BMMCs is comparable to CD45-deficient BMMCs. This unexpected phenotype most likely is due to attenuated interaction between CD45 E613R and Lyn and a hyper-activation of the Fyn-regulated phosphatidylinositol-3-kinase pathway. Interestingly, depending on the receptor system addressed, CD45-deficient and CD45 E613R BMMCs show uniform phenotypes as well. Proliferation of both cell types in response to IL-3 and/or SF is enhanced compared to WT BMMCs. Together, the data indicate that CD45 plays a complex and essential role in fine-tuning mast cell responses mediated by different ligand-receptor systems.
authors.affiliation: Molecular Immunology, Institute for Biology III, University of Freiburg & Max-Planck-Institute for Immunobiology, Freiburg, Germany.
authors.forename: Gordon
authors.initials: G
authors.lastname: Grochowy
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Hermiston
authors.forename: Marcel
authors.initials: M
authors.lastname: Kuhny
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
authors.forename: Michael
authors.initials: M
authors.lastname: Huber