RESUMO
A Disintegrin and Metalloproteinase (ADAM)-10 plays critical roles in neuronal migration and distribution. Recently, ADAM10 deletion was shown to disrupt myelopoiesis. We found that inducible deletion of ADAM10 using Mx1-driven Cre recombinase for a period of three weeks resulted in mast cell hyperplasia in the skin, intestine and spleen. Mast cells express surface ADAM10 in vitro and in vivo, at high levels compared to other immune cells tested. ADAM10 is important for mast cell migration, since ADAM10-deficiency reduced c-Kit-mediated migration. As with some mast cell proteases, ADAM10 expression could be altered by the cytokine microenvironment, being inhibited by IL-10 or TGFß1, but not by several other T cell-derived cytokines. Collectively these data show that the ADAM10 protease is an important factor in mast cell migration and tissue distribution, and can be manipulated by environmental cues.
Assuntos
Proteínas ADAM/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Movimento Celular/genética , Mastócitos/fisiologia , Proteínas de Membrana/metabolismo , Fator de Células-Tronco/metabolismo , Proteínas ADAM/biossíntese , Proteínas ADAM/genética , Proteína ADAM10 , Secretases da Proteína Precursora do Amiloide/biossíntese , Secretases da Proteína Precursora do Amiloide/genética , Animais , Proliferação de Células , Células Cultivadas , Hiperplasia/genética , Interleucina-10/farmacologia , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peritônio/citologia , Interferência de RNA , RNA Interferente Pequeno , Linfócitos T/imunologia , Fator de Crescimento Transformador beta/farmacologiaRESUMO
Mast cells are well known as principle effector cells of type I hypersensitivity responses. Beyond this role in allergic disease, these cells are now appreciated as playing an important role in many inflammatory conditions. This review summarizes the support for mast cell involvement in resisting bacterial infection, exacerbating autoimmunity and atherosclerosis, and promoting cancer progression. A commonality in these conditions is the ability of mast cells to elicit migration of many cell types, often through the production of inflammatory cytokines such as tumor necrosis factor. However, recent data also demonstrates that mast cells can suppress the immune response through interleukin-10 production. The data encourage those working in this field to expand their view of how mast cells contribute to immune homeostasis.
