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Suspension-cultured mouse plasmacytoma cells (MPC-11) were accumulated in the late G1 phase by exposure to isoleucine-deficient medium for 20-24 h. The arrested culture was fed with complete medium enabling the cells to continue the cell cycle synchronously, undergo mitosis, and enter a second cycle of growth. This method of synchronization left the protein-synthesizing ability intact as judged by the polysome profile and the capacity of the cells to incorporate labeled amino acids into protein after the restoration of isoleucine. After incubation in isoleucine-deficient medium and the addition of isoleucine to the culture, cells entered the S phase after a short lag, as judged by [SH]thymidine incorporation into nucleic acid and by spectrophotometric measurement of nuclear DNA. The cells were in mitosis between 12 and 18 h as judged by the increase in cell count and analysis of cell populations on albumin gradients.Synthesis and secretion of light-chain immunoglobulin were maximal in the late G1/early S phase of the first cycle. During late S phase, G2 phase, and mitosis, both synthesis and secretion were observed to be at a low level; however, immediately after mitosis the cells which then entered the G I phase apparently commenced synthesis of light chain immunoglobulin straight away, although secretion of labeled material remained at a low level.Lymphocytes ordinarily are quiescent cells that produce little or no immunoglobulin. After stimulation by antigen, lymphocytes undergo a transition to active, immunoglobulin-producing cells. Several investigators, using immunoglobulinsecreting, tissue-cultured cells which had been synchronized by different techniques, have suggested that the bulk of immunoglobulin synthesis occurs in the late G l/early S phase of the cell cycle (4,5,16,20), while other observations have not demonstrated any cyclical behavior with respect to immunoglobulin synthesis (6, 13).As part of studies concerned with elucidating the details of immunoglobulin biosynthesis and of membrane biogenesis on a molecular level, it became important to isolate large quantities of 232

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Total serum IgE and eosinophil count were determined for 30 patients with intolerance to aspirin. Total IgE levels in the aspirin intolerant patients were similar to those expected in a non-atopic population. In contrast, total eosinophil count (TEC) tended to be elevated in the aspirin intolerant group. Elevated TEC was observed both in bronchospastic (57%) and in urticarial (25%) aspirin intolerance. Specific anti-aspiryl and anti-tartrazyl antibodies of the IgE class were assayed by the galactosidase immunosorbent test (GIST). IgE anti-aspiryl antibodies were possibly detected in one patient, but did not correlate with clinical intolerance to aspirin. It is unlikely that the clinical symptoms and the eosinophilia of intolerance to aspirin and tartrazine are mediated by antibodies of the IgE class.

Interleukin-5 (IL-5) is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of TH2 cells leads to the production of IL-5. The proeosinophilic effects of IL-5 include 1) enhanced replication and differentiation of eosinophilic myelocytes; 2) enhanced degranulation of eosinophils; 3) prolonged survival time of eosinophils; and 4) enhanced adhesion of eosinophils. The effects of IL-5 are mediated via the interaction of IL-5 with receptors (Il-5R) expressed on the eosinophil cell membrane. Intracellular signaling produced by occupation of the IL-5R by IL-5 occurs via the JAK-STAT system. IL-5 is a 45kD glycoprotein that consists of two identical polypeptide chains. The 5'-promoter region of the IL-5 gene contains elements that are down-regulated by glucocorticoids. A 16-mer deoxyoligonucleotide, antisense to IL-5 mRNA and with two phosphorothioate modifications, produced, at 20 micromolar concentration, complete inhibition of IL-5 secretion by human peripheral blood mononuclear cells. The targeted 16-mer sequence of the IL-5 mRNA did not display complete homology with any other known human gene sequences. These results suggest that the 16-mer phosphorothioate antisense IL-5 provides the basis for a non-glucocorticoid, sequence-specific inhibitor of IL-5.

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IL-5 is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of Th-2 cells leads to the production of IL-5. The pro-eosinophilic effects of IL-5 include: (1) enhanced replication and differentiation of eosinophilic myelocytes; (2) enhanced degranulation of eosinophils; (3) prolonged survival time of eosinophils: and (4) enhanced adhesion of eosinophils. The effects of IL-5 are mediated via the interaction of IL-5 with receptors (IL-5R) that are expressed on the eosinophil cell membrane. Intracellular signalling produced by occupation of the IL-5R by IL-5 occurs via the JAK-STAT system. IL-5 is a 45 kDa glycoprotein consisting of two identical polypeptide chains. The 5'-promoter region of the IL-5 gene contains elements that are down-regulated by glucocorticoids. Anti-IL-5 reagents have the potential to suppress IL-5 activity without the side effects of glucocorticoids. Studies using monoclonal antibodies (mAbs) against IL-5 have established the feasibility of suppressing eosinophilic inflammation by specifically blocking IL-5 activity. Studies with antisense IL-5 are beginning to provide the basis for non-glucocorticoid, sequence-specific oligonucleotide inhibitors of IL-5. Research has begun on the development of mAbs and antisense oligonucleotide inhibitors of IL-5 that can be inhaled and applied topically.