The role of granulocyte macrophage-colony stimulating factor in the regulation of anaphylactic reactions

Abstract

Granulocyte-macrophage colony stimulating factor (GM-CSF) is one of the hematopoietic cytokines that affect differentiation and survival of myeloid lineage cells. Recently, GM-CSF has drawn attention as an inflammatory cytokine because of its prominent role in both autoimmune diseases and allergic diseases. However, the relationship between GM-CSF and anaphylaxis has not been clearly elucidated. To investigate this, I established two ovalbumin (OVA)-induced anaphylaxis models in C57BL/6 mice. One employed alum as an adjuvant, and the other utilized GM-CSF. In the model sensitized with alum, mild anaphylactic reactions were observed after both local or subcutaneous injection of OVA and systemic or intravenous injection of OVA. Meanwhile, in the model sensitized with GM-CSF, anaphylactic reactions were only observed upon systemic OVA challenge but not local injection. These systemic anaphylactic reactions were further aggravated when the number of sensitization with GM-CSF increased. Along with the intensified anaphylaxis, the levels of total IgE, OVA-specific IgE and OVA –specific IgG were elevated. Then I examined the change of leukocyte populations over time in the spleen and peritoneal cavity following treatment with GM-CSF. Significant basophilia was observed in the spleen, whereas the number of mast cells was not altered in the spleen and peritoneal cavity. Besides, in the peritoneal cavity, the numbers eosinophils and small peritoneal macrophages increased while the number of large peritoneal macrophages decreased. Therefore, for the first time, the distinct anaphylactic features in humoral and cellular aspects of immune responses are revealed by treatment with GM-CSF. All in all, the study suggests that GM-CSF-induced strong basophilia in the spleen might play an important role in the systemic anaphylaxis, which has not been recognized previously.