Histamine-Releasing Factor and Immunoglobulins in Asthma and Allergy

Factors that can induce the release of histamine from basophils have been studied for more than 30 years. A protein termed histamine-releasing factor (HRF) was purified and molecularly cloned in 1995. HRF can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells. HRF-like activities were found in bodily fluids during the late phase of allergic reactions, implicating HRF in allergic diseases. However, definitive evidence for the role of HRF in allergic diseases has remained elusive. On the other hand, we found effects of monomeric IgE on the survival and activation of mast cells without the involvement of a specific antigen, as well as heterogeneity of IgEs in their ability to cause such effects. The latter property of IgE molecules seemed to be similar to the heterogeneity of IgEs in their ability to prime basophils in response to HRF. This similarity led to our recent finding that ~30% of IgE molecules can bind to HRF via their Fab interactions with two binding sites within the HRF molecule. The use of peptide inhibitors that block HRF-IgE interactions revealed an essential role of HRF to promote skin hypersensitivity and airway inflammation. This review summarizes this and more recent findings and provides a perspective on how they impact our understanding of allergy pathogenesis and potentially change the treatment of allergic diseases.

Most Highly Cytokinergic IgEs Have Polyreactivity to Autoantigens

PURPOSE: Monomeric IgE molecules, when bound to the high-affinity receptor, exhibit a vast heterogeneity in their ability to induce survival promotion and cytokine production in mast cells. At one end of this spectrum, highly cytokinergic (HC) IgEs can induce potent survival promotion, degranulation, cytokine production, migration, etc., whereas at the other end, poorly cytokinergic (PC) IgEs can do so inefficiently. In this study, we investigated whether IgEs recognize autoantigens and whether IgEs' binding of autoantigens correlates with difference s in HC versus PC properties. METHODS: Enzyme-linked immunosorbent assays were performed to test whether IgEs bind antigens. Histamine-releasing factor in human sera was quantified by western blotting. Cultured mast cells derived from human cord blood were used to test the effects of human sera on cytokine production. RESULTS: Most (7/8) of mouse monoclonal HC IgEs exhibited polyreactivity to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), beta-galactosidase, thyroglobulin and/or histamine-releasing factor. By contrast, mouse PC IgEs failed to react with these antigens. A human monoclonal HC IgE also showed polyreactivity to histamine-releasing factor, dsDNA and ssDNA. Interestingly, sera from atopic dermatitis patients showed increased reactivity to ssDNA and beta-galactosidase and increased levels of histamine-releasing factor. Some atopic dermatitis patients, but not healthy individuals, had substantial serum levels of HRF-reactive IgE. Sera from atopic dermatitis patients with high titers of DNA-reactive IgE could induce several fold more IL-8 secretion in human mast cells than sera from healthy individuals. CONCLUSIONS: The results show that most HC, but not PC, IgEs exhibit polyreactivity to autoantigens, supporting the autoimmune mechanism in the pathogenesis of atopic dermatitis.

Pararectal versus Transverse Incision for Retroperitoneal Approach to Aorto-Iliac Region / 日本心臓血管外科学会雑誌

Two types of skin incision, pararectal and transverse, in the retroperitoneal approach to aorto-iliac region were compared. For the last 3 years, 34 abdominal aortic aneurysms, excluding ruptured cases, and 43 cases of aorto-iliac occlusive disease were all operated on by a retroperitoneal approach in our hospital. Of these, 36 patients underwent pararectal incision (P group) and 41 patients transverse incision (T group). An Octopus^® retractor yielded a wide operative field in all cases. The mean interval from the start of the operation to the aortic cross clamp were almost equal in the two groups (89.7 and 91.1 minutes). The mean amount of intraoperative bleeding was significantly smaller in the T group (749ml) than in the P group (1, 096ml). The mean interval after surgery to beginning peroral alimentation, weaning from analgesics and discharge from the hospital were all significantly shorter in the T group (1.6, 3.3 and 10.8 days) than the P group (2.8, 4.8 and 15.8 days). Transverse incision for a retroperitoneal approach to the aorto-iliac region is preferable for an early recovery and short hospital stay.

Operative Procedure of Exclusion and Bypass Grafting for Infected Abdominal Aortic and Iliac Artery Aneurysms / 日本心臓血管外科学会雑誌

A 69-year-old man was admitted because of pyrexia and increased ESR and CRP. Blood culture was positive for Staphylococcus, and CT scan and aortography revealed irregularly shaped abdominal aortic and left common iliac artery aneurysms which grew rapidly. An urgent operation with exclusion and bypass grafting was performed because aneurysms tightly adhered to the surrounding tissues and dissection appeared to be extremely difficult. Administration of antibiotics was continued intravenously, then orally for three months postoperatively, and pyrexia and the increased ESR and CRP disappeared.