IgE receptor-mediated release of nerve growth factor by mast cells

Background It has previously been demonstrated that the level of nerve growth factor (NGF) is increased in serum from humans with allergic diseases and asthma. Aim A question raised by these observations is whether NGF could be released from degranulating mast cells during an allergic reaction. The aim of this study was to investigate if NGF is released from mast cells after activation through cross-linkage of the high-affinity IgE receptor. Methods Mouse and human in vitro cultured mast cells were activated by IgE and specific antigen, stem cell factor or lipopolysaccharide. Release of NGF was measured by ELISA and mRNA expression was detected by RT PCR. Results We found that mast cells not only express NGF transcripts, but also release NGF polypeptide in response to IgE and specific antigen. Activation of mouse mast cells for 30 min induced significant release of NGF (32.9 +/- 1.3 pg/2 x 10(6) cells) compared to spontaneous release (13.9 +/- 2.7 pg/2 x 10(6) cells) (P < 0.01). Similarly, activation of human cultured mast cells also resulted in a significant increase of NGF release (733 +/- 310 pg/3 x 10(5) cells) compared to spontaneous release (9.2 +/- 4.0 pg/3 x 10(5) cells). Two other mast cell secretogogues studied, stem cell factor and lipopolysaccharide, were not able to induce release of NGF. Conclusion This study provides evidence that NGF could be specifically released by stimuli causing an allergic reaction, and mast cells can thereby be the source of NGF in IgE-mediated allergic diseases. Our findings add further support for a close correlation between NGF and mast cells that could be of importance for the allergic inflammation.