[Immunolocalization of HB-EGF in human atherosclerotic plaques]. / Immunolocalizzazione di HB-EGF in placche aterosclerotiche umane.

AIMS: Heparin-binding epidermal growth factor is a member of the EGF family, it is a potent mitogen for smooth muscle cells and has been implicated in atherosclerosis, angiogenesis. In athererogenesis, HB-EGF has been detected in medial smooth cells and foamy macrofages. In this work, we have investigate about immunohistocemical localization of HB-EGF in atherosclerotic plaques. MATERIALS AND METHODS: Three cases of man affected by atherosclerosis have been examined. We have collected and examined atherosclerotic plaques by immunohistochemical procedure in optical microscopy. Samples have been incubated with primary Ac (anti-human HB-EGF- goat IgG). RESULTS: In the three examined cases, results are partly overlap-ping, but with some difference in relation to location of positivity to HB-EGF. Only in one case, HB-EGF staining is rather weak and located just below endothelium where is a thickened area of tissue rich in fibres and few cells, In another case, positivity to HB-EGF is present in an area of connective tissue of the intima. In the last case, positivity to HB-EGF is evident in the context of a presumed elastic tissue with fusiform cells following fibres orientation, and that could be fibroblasts or smooth muscle cells. CONCLUSIONS: These results indicate that HB-EGF is involved in the development of atherosclerotic plaques and that HB-EGF is a possible target for atherosclerosis therapy.

Prolactin increases HO-1 expression and induces VEGF production in human macrophages.

The pituitary hormone prolactin (PRL) is a multifunctional polypeptide which exerts a role on cell proliferation and may also contribute to cell differentiation. PRL is also produced by immune cells and is regarded as a key component of the neuroendocrine-immune loop and as a local regulator of macrophage response. The involvement of PRL in regulating monocyte/macrophage functions is suggested by the presence of PRL receptors in these cells. It has been shown that PRL possess both angiogenic and antiangiogenic effects. Recently, we revealed that augmentation of HO-1 activity enhances PRL-mediated angiogenesis in human endothelial cells. Since macrophages are key participants in angiogenesis our objective was to investigate the effect of PRL also in human macrophages. In vitro treatment of macrophages with PRL was found to increase both heme oxygenase-1 (HO-1) expression and protein synthesis in a time and dose dependent manner as quantified respectively by reverse-transcriptase real-time polymerase chain reaction and Western blot analysis. PRL-treated macrophages also showed an enhanced release of vascular endothelial growth factor (VEGF) as demonstrated by ELISA assay. Furthermore, to determine whether PRL-induced HO-1 activity was required for VEGF production by macrophages, the effect of PRL on the induction of VEGF was studied in the presence of an inducer stannic chloride (SnCl(2)) and of an inhibitor stannic mesoporphyrin (SnMP) of HO activity. Our observations suggest that PRL may regulate monocyte activation and influences not only immune function but also angiogenesis.

Early events of secretory granule formation in the rat parotid acinar cell under the influence of isoproterenol. An ultrastructural and lectin cytochemical study.

The events involved in the maturation process of acinar secretory granules of rat parotid gland were investigated ultrastructurally and cytochemically by using a battery of four lectins [Triticum vulgaris agglutinin (WGA), Ulex europaeus agglutinin I (UEA-I), Glycine max agglutinin (SBA), Arachys hypogaea agglutinin (PNA)]. In order to facilitate the study, parotid glands were chronically stimulated with isoproterenol to induce secretion. Specimens were embedded in the Lowicryl K4M resin. The trans-Golgi network (TGN) derived secretory granules, which we refer to as immature secretory granules, were found to be intermediate structures in the biogenesis process of the secretory granules in the rat parotid acinar cell. These early structures do not seem to be the immediate precursor of the mature secretory granules: in fact, a subsequent interaction process between these early immature granule forms and TGN elements seems to occur, leading, finally, to the mature granules. These findings could explain the origin of the polymorphic subpopulations of the secretory granules in the normal acinar cells of the rat parotid gland. The lectin staining patterns were characteristic of each lectin. Immature and mature secretory granules were labelled with WGA, SBA, PNA, and lightly with UEA-I. Cis and intermediate cisternae of the Golgi apparatus were labelled with WGA, and trans cisternae with WGA and SBA.

Immunosenescence and cancer: a review.

The human neoplastic pathologies are age-dependent. The increased occurrence of tumors observed with advancing age may be determined by the accumulation of certain phenomena promoting different phases of neoplastic processes. In these events, important roles can be attributed to mutations of the genome that accumulate during aging and to the immunosenescence. It may be hypothesized that certain tumors controlled by the immune system may become more frequent in the elderly as a consequence of the decreased functionality of this important defense system of the organism. Nevertheless, the problems of the interrelationships between the immunosenescence and tumors are seriously contradictory. Therefore, on the one hand, one has to establish how much the immunodeficit of the elderly patient may be responsible for the neoplastic pathology, while on the other hand, one cannot neglect important environmental and pathophysiological factors in these cases.

Immunosenescence: a review.

Aging involves the morphological and functional integrity of all organs, including the cellular and humoral immunological functions. The main alterations can be listed as follows: (i) Thymic involution resulting in the decreased number of lymphoid precursor T- and B-cells. (ii) Reduced proliferative capacity of T-cells; loss of lymphocyte subgroups as a consequence of the shortening of telomeres. (iii) Qualitative deficiency of B-lymphocytes with a reduced response to exogenous antigens. (iv) Compromised activity of the accessory cells, both directly by depressing the chemotactic and phagocytic responses, and indirectly by increasing the prostaglandin production which inhibit the proliferation of T-cells. (v) Alterations in the production and secretion of various cytokines. (vi) Other factors like the general physiological conditions, the nutritional state, psychological habit and various hormone levels.

Effects of a tryptophan deficient diet on the morphology of skeletal muscle fibers of the rat. Preliminary observations at neuroendocrinological and submicroscopical levels.

It is proposed an animal model consisting of young male, L-tryptophan-deprived, namely 5-HT-free rats since their ontogenesis. This was obtained by feeding their mothers with a L-tryptophan-free (tf) diet since the day 1 of pregnancy. They were studied and compared with control rats of the same ages fed with a complete diet. Already at birth tf-litters were significantly underdeveloped as compared to the control newborn rats. Postnatal growth was in the tf-rats so poor that it worsened into a stricking dwarfism characterized by physical immaturity, muscular hypotrophy with alterations of motor activity and impairment of the hypothalamo-pituitary-axis. A radioimmunological study of growth hormone (GH) showed in tf-rats dramatic low plasma levels of the hormone, thus confirming the existence of serotonergic hypothalamo-pituitary pathways for GH in normal animals. By histological and ultrastructural examinations, hypotrophy and degenerative alterations of the muscle fibers could be observed. The possible causes for this finding are extensively considered and discussed.