Passive anaphylaxis and IgE antibody production are compromised in tumor necrosis factor- and in granulocyte-macrophage colony stimulating factor-deficient mice

ABSTRACT Background A number of recent studies has demonstrated a critical role for mast cells and mast cell-derived cytokines, especially tumour necrosis factor (TNF), in the control of host defense mechanisms during inflammation. In the presesnt study, we investigated whether TNF-deficient (TNF −/− ) and granulocyte-macrophage colony stimulating factor (GM-CSF)-deficient (GM-CSF −/− ) mice expressed defects in normal mast cell function. Methods Because the first step in the passive cutaneous anaphylactic (PCA) reaction is fixation of the antibody to mast cells, we tried to obtain a PCA in TNF −/− and GM-CSF −/− mice. Results While an anti-dinitrophenyl IgE monoclonal antibody induced a strong PCA reaction in wild-type mice, it was not possible to obtain a PCA reaction in either TNF −/− or GM-CSF −/− mice. We next examined whether mast cells were present in these mice and if so, did they have functional FceRI receptors on their surface. The number of mast cells in smears from the peritoneal fluid of the TNF −/− and GM-CSF −/− mice was similar to that seen in wild-type mice. However, the expression of FceRI on mast cells from the peritoneal fluid of TNF −/− and GM-CSF −/− mice, measured by either rosetting assay or FACScan analysis, was compromised compared with wild-type mice. Previous studies have established that defects in FCeRI expression often have found that IgE production was compromised in both TNF −/− and GM-CSF −/− mice. Conclusions The observed defects may partially explain the immunodeficiency of these cytokine-deficient animals during infection.