The MAGE genes encode certain tumor-associated antigens recognized by cytotoxic T lymphocytes. We investigated the expression of the MAGE-1, -2, -3, -4, -41, and -6 genes in 88 head-and-neck squamous-cell carcinomas (83 fresh tumor samples and 5 cell lines), using a reverse-transcription-polymerase-chain-reaction assay, followed by dot-blot hybridization with sequence-specific oligonucleotides and/or restriction enzyme-pattern analysis. The MAGE-1, -2, -3, -4, -41 and -6 genes were expressed at the mRNA level in 27, 34, 36, 22, 16 and 35, respectively, of 83 fresh tumor samples. At least one of these genes was expressed in 59 of the 83 samples. Neither non-tumor inflammatory cells nor normal tissues were positive for these genes. The MAGE-1 gene was expressed relatively frequently in SCC of the oropharynx, hypopharynx and maxillary sinus, but at lower rates in SCC of the larynx and of the tongue and oral cavity. MAGE-1 was frequently expressed in poorly differentiated SCC, somewhat less frequently in moderately differentiated SCC, and only infrequently in well-differentiated SCC. The expression levels of the other MAGE genes also varied with the anatomic site as well as the degree of differentiation. Our results suggest that specific immunotherapy against MAGE gene products may be useful for patients with head-and-neck carcinomas.

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Substance P (SP) is a tachykinin involved in the regulation of inflammatory processes. To investigate a modulatory role of the neuropeptide SP in allergic inflammation, we studied its priming effect on human eosinophil chemotaxis and kinetic responses towards platelet activating factor (PAF) and recombinant human interleukin 5 (rhIL-5). Blood was obtained from normal subjects and eosinophils were separated by Percoll discontinuous density gradient centrifugation. High purification was obtained by negative selection procedure (CD16-beads) and the experiments were performed in a 48-well microchemotaxis Boyden chamber. In the present study we demonstrate a potent synergistic effect of 1OOnM dose of SP on the migratory function of human eosinophils stimulated by PAF and rhIL- 5. This synergism was chemotaxis specific and was abolished by NK-1 receptor antagonist (FK888). The results suggest that neurogenic stimuli may play a significant role in eosinophil infiltration via its priming effect on the cell.

Background: Eosinophil granule proteins deposition at the site of allergic inflammation contributes to the late-phase reaction of hypersensitivity diseases. In the present communication, we describe the effect of human eotaxin on normal human eosinophil exocytosis measured as degranulation of eosinophil-derived neurotoxin (EDN). Methods: Purified eosinophils were obtained from normal healthy volunteers with the CD16-negative procedure. Purified eosinophils were stimulated with various concentrations of eotaxin and the amount of EDN released was analysed by radioimmunoassay. Flow cytometry was used to examine the surface expression of adhesion molecules on eosinophils. Results: Eotaxin significantly induced EDN release in a dose-dependent manner. The potency of eotaxin in this effect was equal to that of RANTES, and comparable to that of platelet-activating factor. Eotaxin-induced EDN release was blocked by cytochalasin B in a dose-dependent manner. The surface expression of CD11a, CD11b, CD18 and VLA-4 adhesion molecules on normal human eosinophils were not modulated by eotaxin stimulation. Conclusions: These results indicate that eotaxin may play an important role not only as a selective chemotaxin for the cell type but also as a secretagogue. Furthermore, they demonstrate a degranulation mechanism(s) involving cytoskeletal changes which is probably independent of the quantitative expression of adhesion molecules.

Eosinophils and neuropeptides are thought to play effector roles in allergic diseases, such as rhinitis; however, little is known about the biological effects of neuromediators, especially vasoactive intestinal peptide (VIP), on eosinophil functional responses. In the present study, it is shown that VIP induces eosinophil chemotaxis and eosinophil-derived neurotoxin (EDN) release in potency comparable with that induced by platelet activator factor, and in a novel synergistic manner with recombinant human interleukin-5. Contrary to chemotaxis, EDN release was sensitive to staurosporine, the protein kinase C inhibitor, as well as intracellular calcium chelation. However, eosinophil treatment with inhibitors of tyrosine kinases (herbimycin A) and phosphatases (pervanadate) resulted in a dose-dependent potentiation and blockage of VIP-induced eosinophil chemotaxis, respectively. Treatment of eosinophils with VIP receptor antagonist did not modify VIP-induced chemotaxis or EDN release. Furthermore, exploration of vasoactive intestinal peptide receptor I expression was lacking in human eosinophils, but not lymphocytes. These results demonstrate two different mechanisms in triggering eosinophil activation of functional responses by VIP, a calcium-dependent degranulation and a calcium-independent chemotaxis, and elaborate on a novel cytokine-neuropeptide interaction in eosinophilic inflammation.