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lüll Human airway smooth muscle promotes human lung mast cell survival, proliferation, and constitutive activation: cooperative roles for CADM1, stem cell factor, and IL-6 Hollins F; Kaur D; Yang W; Cruse G; Saunders R; Sutcliffe A; Berger P; Ito A; Brightling CE; Bradding PJ Immunol 2008[Aug]; 181 (4): 2772-80The microlocalization of mast cells within specific tissue compartments is thought to be critical for the pathophysiology of many diverse diseases. This is particularly evident in asthma where they localize to the airway smooth muscle (ASM) bundles. Mast cells are recruited to the ASM by numerous chemoattractants and adhere through CADM1, but the functional consequences of this are unknown. In this study, we show that human ASM maintains human lung mast cell (HLMC) survival in vitro and induces rapid HLMC proliferation. This required cell-cell contact and occurred through a cooperative interaction between membrane-bound stem cell factor (SCF) expressed on ASM, soluble IL-6, and CADM1 expressed on HLMC. There was a physical interaction in HLMC between CADM1 and the SCF receptor (CD117), suggesting that CADM1-dependent adhesion facilitates the interaction of membrane-bound SCF with its receptor. HLMC-ASM coculture also enhanced constitutive HLMC degranulation, revealing a novel smooth muscle-driven allergen-independent mechanism of chronic mast cell activation. Targeting these interactions in asthma might offer a new strategy for the treatment of this common disease.|*Cell Proliferation[MESH]|Cell Adhesion Molecule-1[MESH]|Cell Adhesion Molecules[MESH]|Cell Adhesion/immunology[MESH]|Cell Communication/*immunology[MESH]|Cell Movement/immunology[MESH]|Cell Survival/immunology[MESH]|Cells, Cultured[MESH]|Coculture Techniques[MESH]|Humans[MESH]|Immunoglobulins/*physiology[MESH]|Interleukin-6/*physiology[MESH]|Mast Cells/cytology/*immunology/metabolism[MESH]|Membrane Proteins/*physiology[MESH]|Muscle, Smooth/cytology/*immunology[MESH]|Respiratory Mucosa/cytology/*immunology/metabolism[MESH]|Stem Cell Factor/*physiology[MESH]|Tumor Suppressor Proteins/*physiology[MESH] |