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Carbohydrate antigen CA 15-3 is a glycoprotein whose expression, aberrant intracellular localization and changes in glycosylation have been associated with a wide range of cancers. Pulmonary fibrosis represents the final evolution of a chronic inflammation and is defined by the overgrowth of fibroblasts and exaggerated extracellular matrix deposition. The aim of the present study was to evaluate the possible diagnostic role of CA 15-3 in fibrosis in different idiopathic interstitial pneumonias.CA 15-3 was measured in serum samples from healthy subjects (n=25) and patients affected with idiopathic pulmonary fibrosis (IPF/UIP) (n=20), sarcoidosis (n=22) at different stages (I, II, and III) and systemic sclerosis (n=25). CA 15-3 protein expression was also evaluated by immunohistochemistry in 21 lung biopsies and in 6 primary lung fibroblasts cell lines.The CA 15-3 serum levels were significantly higher in patients with IPF/UIP and with clinically advanced sarcoidosis (stage III). Serum CA 15-3 levels were slightly increased in patients with systemic sclerosis. No difference was observed between serum CA 15-3 levels in patients with sarcoidosis at stages I and II compared with control subjects. In IPF/UIP and in sarcoidosis at stage III elevated CA 15-3 serum levels significantly correlated with decreased total lung capacity, decreased diffusing capacity of carbon monoxide and high resolution computed tomography findings. Immunohistochemical analysis showed an intense specific CA 15-3 staining in fibroblasts within fibroblastic foci, surrounding sarcoid granulomas and in all cell cultures of lung fibroblasts from IPF/UIP lungs.Our results indicate that increased CA 15-3 levels are associated with pulmonary interstitial damage, fibroblast activity and progression to fibrosis of the lung. Therefore, CA-15-3 may be considered a sensitive marker useful in the identification of patients with advanced fibrosis and more severe prognosis.

Lymphoid organs are supplied by many nerve endings associated with different kinds of cells and macrophages. The role of this innervation on the release of locally active molecules is still unclear. Lingual tonsils belong to Waldeyer's Ring, in close association with palatine tonsils and nasopharyngeal (adenoids) tonsils, thus constituting part of NALT (nasal-associated lymphoid tissue) together with the tubal tonsils and lateral pharyngeal bands. In this study, we focused our attention on the expression of some neurotrophins (NTs) and their high- and low-affinity receptors in human lingual tonsils. Light immunohistochemistry showed that human tonsillar samples were generally positive for all the NTs investigated (NGF, BDNF, NT-3, NT-4) and their receptors (TrKA, TrKB, TrKC and p75) with some different expression levels. NGF and TrKC were strongly expressed in macrophages, but weakly in lymphocytes. However, BDNF and TrKB was highly expressed in lymphocytes and weaker in macrophages. The low-affinity receptor for NGF, p75, was mainly moderately expressed in the analysed samples. These results suggest the presence of a pattern of neurotrophin innervation in the human lingual tonsil which may play a role in sustaining inflammatory conditions and in modulating a close interaction between the nervous system and the different immune cellular subtypes.

Antidromic stimulation of the rat trigeminal ganglion triggers the release of substance P (SP) and calcitonin gene-related peptide (CGRP) from sensory nerve terminals of the capsaicin sensitive C-fibers. These pro-inflammatory neuropeptides produce a marked hyperemia in the anterior segment of the eye, accompanied by increased intraocular pressure, breakdown of the blood-aqueous barrier and myosis. To assess the effects of neurogenic inflammation on the retina, specifically on the immunostaining of neurotransmitters and neurotrophins, as well as on the expression of neurotrophin receptors in the retina. RT-PCR was also accomplished in control and stimulated animals to confirm the immunohistochemical results. In the electrically stimulated eyes, immunostaining for SP, CGRP, VIP and nNOS demonstrated a marked increase in the RPE/POS (Retinal Pigment Epithelium/Photoreceptor Outer Segments), in the inner and outer granular layers and in the ganglion cells in comparison to the control eyes. CGRP and SP were found increased in stimulated animals and this result has been confirmed by RT- PCR. Changes in neurotrophin immunostaining and in receptor expression were also observed after electric stimulation of trigeminal ganglia. Decrease of BDNF and NT4 in the outer and inner layers and in ganglion cells was particularly marked. In stimulated rat retinas immunostaining and RT-PCR showed a NGF expression increase. Neurotrophin receptors remained substantially unchanged. These studies demonstrated, for the first time, that antidromic stimulation of the trigeminal ganglion and subsequent neurogenic inflammation affect immunostaining of retinal cell neurotransmitter/neuropeptides and neurotrophins as well as the expression of neurotrophin receptors.

Lonidamine (LND) or [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid] is an anticancer and antispermatogenic drug that exerts a large number of effects on tumor cells and germ cells. Sexually mature male Sprague-Dawley rats were housed at 22 degrees C on a 12-h light/12-h dark cycle 1 week before the experiments, with free access to food and water. LND was suspended in 0.5% methylcellulose at a concentration of 10 mg/mL and administered orally at the dose of 10 mL/kg (b.w.) as a single dose. Control rats received an equal amount of vehicle. Testes were removed, fixed for 24 h in 2% glutaraldehyde and 2% paraformaldehyde in 0.1 M sodium phosphate (pH 7.2 at 22 degrees C), rinsed with the same buffer, and stored at room temperature. From each sample, a block of tissue was removed by sectioning through the organ. After dehydration in ethanol at increasing concentrations (70-100%), each block was embedded in paraffin and serial 5 mm thick sections were cut using a rotatory microtome. The immunoreactivity for NTs has been observed in spermatogonia of untreated rats, while the rats treated with LND showed an immunohistochemical localization in all the stages of germinal cells. The generally well-expressed immunoreactivity for the neurotrophins receptors in treated rats observed in our study is presumably attributable to alterations of the receptors' structure and/or expression leading to changes of the activity, affinity, localization or protein interactions that may depend on sensitization of ion channels (induced by LND). Neurotrophins (NTs) appear to be interesting proteins for the modulation of sperm maturation and motility with a prominent role for the nerve growth factor (NGF), that may exert an autocrine or paracrine role. We therefore investigated the location and distribution of immunoreactivity for some neurotransmitters (SP, VIP, CGRP, nNOS, Chat), neurotrophins (NGF, BDNF, NT-3) and their own receptors (TrKA, TrKB, TrKC, p75) in the seminiferous tubules of male rats treated by LND in the light of the literature on this topic.

To the Editor: Ricci et al1 reported that human peripheral blood lymphocytes express α1-adrenergic receptor subtypes. The authors present results of radioligand binding assays with [3H]-prazosin as the radioligand for α1-adrenergic receptors, showing that the maximal density of the binding sites is 175 fmol per 106 cells. This would mean that the actual number of receptors per cell would be exactly 100 000, which is an unusually high number of receptors. Cell lines that are known for their high expression of α1-adrenergic receptors have been reported to express 10 000 to 25 000 receptors per cell.2 3 We have to keep in mind, however, that these numbers are found on kidney or smooth muscle cells, which are much larger than the freshly isolated lymphocytes that were used in the study by Ricci. Moreover, it is known for other G-protein–coupled receptors, eg, β2-adrenergic receptors, that are expressed on lymphocytes that the actual number of receptors per cell is around 2000.4 Thus, the number reported by Ricci et al for α1-adrenergic receptors on lymphocytes is extraordinary high. The authors do cite the literature on α1-adrenergic receptor expression in peripheral blood lymphocytes only partly correct. The only study that reports α1-adrenergic receptor binding on lymphoid cells from peripheral blood is the study by Jetschmann et al.5 However, these authors only examined NK cells where they reported the presence of 600 to 700 receptors per cell. Casale at al6 could not demonstrate binding sites on peripheral blood lymphocytes, whereas Maestroni et al7 only investigated α1-receptor expression …