Akimoto K

Extracellular ATP stimulates interleukin-dependent cultured mast cells and eosinophils through calcium mobilization.

We examined the effect of ATP and related nucleotides on the changes in intracellular calcium ([Ca2+]i) in murine bone marrow-derived mast cells (BMMC) and human cord blood-derived eosinophils (EO) cultured in the presence of interleukins. ATP, ADP and AMP released a substantial amount of histamine and leukotriene C4 from BMMC, and EO showed locomotive activity in response to ATP, ADP and GTP. These reactions were accompanied with an increase in [Ca2+]i in BMMC and in EO. The rise in [Ca2+]i in BMMC induced by ATP or antigen at optimal concentrations was inclined to be persisting. On the other hand, these nucleotides induced a rapid and transient rise in [Ca2+]i in EO. Purified human peripheral EO also exhibited locomotive activity and an increase in [Ca2+]i in response to ATP. These results indicate that extracellular ATP activates interleukin-dependent cultured mast cells and EO through Ca2+ mobilization, and suggest that ATP, which is known to be released from activated platelets or autonomic nerves, may stimulate in vivo counterparts of these cultured inflammatory cells.

How to Prevent Allergic Disease

We have investigated methods for decreasing the number of allergic patients and have produced the following data. We compared mothers’ total IgE levels and allergen-specific IgG and IgG4 levels in 72

Role of chemical mediators after antigen and exercise challenge in children with asthma

Changes in chemical mediators after antigen challenge and exercise challenge tests were studied in children with asthma. Chemical mediators studied after antigen challenge and exercise challenge included histamine, leukotrienes (LTB4, LTC4, and LTD4), and neutrophil chemotactic factor of anaphylaxis (NCA). The pharmacologic modification of immediate and late-phase reactions was evaluated for procaterol (beta 2-agonist), cromolyn sodium, and prednisolone. Histamine levels were noted to rise in patients who had a dual response of a mild to moderate nature, but did not change in patients who had severe asthma. During exercise challenge cromolyn sodium inhibited both immediate and late-phase reactions but also inhibited plasma generation of NCA. Prednisolone, on the other hand, did not affect immediate reactions, but blocked late-phase reactions to exercise and also decreased NCA generation. Procaterol inhibited the generation of LTD4 and also inhibited NCA when compared with placebo. Exercise challenge did not alter levels of plasma histamine or of LTB4 or LTC4.

Release of High Molecular Weight-Neutrophil Chemotactic Activity from Human Tissues, Cells and Secretion

Release of high molecular weight-neutrophil chemotactic activity from human tissues, cells and secretion was studied in vivo and in vitro. Lung, nasal turbinate, nasal polyps, skin of neurofibromatosis, basophils from chronic myeloid leukemia and cultured basophilic cells from cord blood released this mediator following calcium ionophore, antigen, anti-IgE or homogenization in vitro. Its release was also demonstrated in human nasal secretions from patients with allergic rhinitis following antigen challenge. Regarding mononuclear cells no release of this mediator was observed from normal donors or asthmatic patients having no active attack upon challenge with calcium ionophore, phytohemagglutinin or antigen. Homogenized duodenum released high molecular weight-neutrophil chemotactic activity but less activity in comparison with other tissues or cells mentioned above.