Leukemia inhibitory factor is synthesized and released by human eosinophils and modulates activation state and chemotaxis

Background: The cytokine leukemia inhibitory factor (LIF) is known to be produced by both inflamed peripheral autonomic nerves and several cell types involved in the regulation of the immune response, We have recently demonstrated that several structural cell types in human airways produce LIF in response to inflammatory stimuli and that LIF augments contractile responses to tachykinins in airway explants. Because the eosinophil is a major effector cell in asthma and often found adjacent to the nerves, we hypothesized that eosinophils produce LIF and that LIF primes and upregulates eosinophil recruitment and function, allowing bidirectional neuroimmune interactions and augmentation of eosinophil-mediated injury. Objective: The purpose of this study was to demonstrate that human eosinophils synthesize and release LIF, to determine the effects of LIF on eosinophil functions (ie, chemotaxis, granule protein release, expression of the activation marker CD69, and apoptosis), and to compare serum LIF levels between atopic and nonatopic individuals, Methods: Reverse-transcription PCR, ELISA, immunocytochemistry, chemotaxis assay, and flow cytometry were used, Results: Peripheral blood eosinophils express LIF and messenger RNA for LIF and LIF receptor, Serum LIF levels were higher in atopic patients with mild asthma than in nonatopic normal donors. Eosinophils from nonatopic donors were stimulated by calcium ionophore to release small amounts of LIF (from almost none to 5.3 +/- 1.8 pg/10(6) cells), Eosinophils from atopic donors showed a 10-fold increase (from 45.1 +/- 38.7 pg/10(6) cells to 414.5 +/- 189.9 pg/10(6) cells), Preincubation of eosinophils with LIF increased eosinophil peroxidase release 4-fold. LIF was not chemotactic for eosinophils but augmented chemotaxis mediated by substance P by 82% and by platelet-activating factor by 31%. LIF did not effect eosinophil apoptosis but increased CD69 expression. Conclusion: LIF has proinflammatory roles in eosinophil-dependent airway disorders.