Fascin-expressing dendritic cells dominate in polymyositis and dermatomyositis.

OBJECTIVE: Dendritic cells (DC) have been reported among inflammatory infiltrating cells in muscle tissue in idiopathic inflammatory myopathies (IIM), but to our knowledge no studies concerning the expression of langerin (CD207) or fascin (markers of immature and mature DC, respectively) in IIM have been published. METHODS: Immunohistochemical analyses of langerin and fascin expression were performed on specimens from normal muscles, as well as those affected by polymyositis (PM) and dermatomyositis (DM). The results were analyzed by Mann-Whitney U test. RESULTS: In PM and DM, fascin-positive cells were numerous in the majority of the studied samples in perimysial, endomysial, and perivascular cellular infiltrates. Sporadic langerin-positive cells were detected. CONCLUSION: Fascin-positive DC predominance in inflammatory infiltrates in myositic muscles confirms the prevalence of mature forms and indicates that there are conditions stimulating DC maturation in both PM and DM. The induction of immunological tolerance by inhibiting DC maturation may be a promising direction for studies of myositis treatment.

[Idiopathic inflammatory myopathies]. / Idiopatyczne miopatie zapalne.

The following disease entities are being included into the idiopathic inflammatory myopathy group (IIM): dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM). These are primary inflammatory muscle diseases with substantial muscle weakening in their course. Everyone of the entities belonging to IIM is possessed of a particular clinical picture, as well as of histological and immunological features. In this paper, there have been briefly described classification, clinical pictures, supplementary diagnostic tests, treatment and up-to date views on IIM etiopathogenesis.

Histamine-induced cyclic AMP formation in the chick hypothalamus: interaction with vasoactive intestinal peptide.

Effects of histamine (HA) on cyclic AMP production and its action upon the effects evoked by vasoactive intestinal peptide (VIP) were studied in the chick hypothalamus. HA (0.1-1000 microM) potently stimulated cyclic AMP formation in the hypothalamic slices, reaching maximal effect (2.5-3.5-fold increase) at a 100 microM concentration, and displaying an EC50 value of approximately 6.5 microM/ The stimulatory action of HA was mimicked by agonists of HA receptors, with the following rank order of potency: HA>4-methylHA (H2)>or=Nalpha,Nalpha-dimethylHA (H3>>H1=H2)>or=2-methylHA (H1)>>amthamine (H2)>>dimaprit (H2) approximately tele-methylHA. The HA (100 microM)-evoked increase in cyclic AMP production was concentration-dependently antagonized by selective H2-HA receptor blockers (aminopotentidine>>cimetidine>or=ranitidine>>zolantadine) and was not affected by mepyramine and thioperamide, a selective H1- and H3-HA receptor antagonist, respectively. The pharmacological profile of HA receptors linked to the cyclic AMP-generating system in the chick hypothalamus indicates that they represent either an avian-specific H2-like HA receptor or a novel subtype of HA receptors. Chicken VIP (cVIP; 0.1-3 microM) potently stimulated cyclic AMP synthesis in the chick hypothalamus in a concentration-dependent manner. A combination of cVIP with HA produced cyclic AMP response more than additive, and such a synergistic interaction was antagonized by ranitidine. It is suggested that in the avian brain HA and VIP may play in concert to regulate neuroendocrine processes.

Can tissue transglutaminase be a marker of idiopathic inflammatory myopathies?

In the normal striated muscle, tissue transglutaminase (TG2) content is vestigial. However, this protein's presence has been reported to occur in myoblasts and myotubes during the fetal period. Its increased expression has been also found in the muscle tissue in the course of sporadic inclusion body myositis, as well as in polymyositis (PM) and dermatomyositis (DM), which are considered to be diseases of immunological origin. Based on in vitro studies, a substantial TG2 role in the infiltration of some T cell subsets into inflamed tissues has been suggested lately. In this study, the immunohistochemical reactions in the guinea pig experimental myositis specimens and in the ones from PM/DM patients were compared. The guinea pig tissue specimens were taken from muscles affected by experimental myositis induced by intramuscular injections of: 1/sera from 30 neoplasm patients with no metastases; 2/sera from 10 healthy people; 3/sera from 2 DM patients; 4/neuropeptides (SP, NPY or VIP) and from 5/the muscles affected by the reversed passive Arthus reaction (RPAR). The immunostaining for TG2 revealed substantial presence of this protein in single, damaged muscle fibers and a weak reaction in regenerating fibers appearing in PM/DM patients' specimens. From among experimental myositis specimens, a very intensive reaction appeared only in the damaged and regenerating muscle fibers present in the slides from guinea pig muscles injected with DM patients' sera. Such results suggest some presence of a specific factor(s) (the one(s) responsible for TG2 expression in the damaged muscle fibers) in DM patients' sera. The results suggest that transglutaminase can be a marker of inflammatory myopathies. A probable correlation between TG2 expression in muscles and organismal immunological factors, including the complement activation status, requires additional studies.

Effect of different forms of vasoactive intestinal peptide on cAMP formation in the mammalian cerebral cortex.

Chicken, guinea pig and mammalian (human/porcine/rat) vasoactive intestinal peptides (VIP; 0.001-3 microM) were compared with respect to their ability to stimulate adenosine 3', 5'-cyclic monophosphate (cAMP) formation in the cerebral cortical slices of rat and guinea pig. Of the tested peptides, i.e. chicken VIP (cVIP), guinea pig VIP (gpVIP) and human/rat/porcine (mammalian) VIP (mVIP), the strongest stimulator of cAMP synthesis was cVIP, and the weakest one - the gpVIP. Pituitary adenylate cyclase-activating polypeptide (PACAP) used as a reference drug at 0.1 microM concentration strongly stimulated cAMP formation in the cerebrum of both species, being, however, significantly more potent in the guinea pig model. The obtained data demonstrate significant differences in biological activity between cVIP and two distinct mammalian VIPs in the cerebral cortex of rat and guinea pig.

Immunolocalization of CGRP, NPY and PGP 9.5 in guinea pig skin.

By means of immunoperoxidase and immune-alkaline phosphatase methods the immunoreactivities to neuropeptides: neuropeptide Y (NPY), calcitonin gene related peptide (CGRP) and a pan-neuronal marker, the protein gene product 9.5 (PGP 9.5), were evaluated in guinea pig deep dorsal skin specimens. CGRP immunoreactive (CGRP-IR) and NPY-immunoreactive (NPY-IR) nerve fibres were dispersed in the papillary dermis and sometimes inside the hair roots and among the sebaceous gland cells. Such localized nerve fibres have not so far been described. In the subcutaneous layer nerve trunks were found composed of CGRP-IR and NPY-IR nerve fibres. Some of these indicated vestigial or negative immunoreactivity to PGP 9.5.

Immunolocalization of protectin (CD59) and macrophages in polymyositis and dermatomyositis.

Immunohistochemical stainings for protectin (CD59) and for the macrophage/monocyte antigen were performed in muscle specimens of polymyositis (PM) and dermatomyositis (DM) patients. In control muscles, a granular immunostaining of CD59 at the surface of 10-15% from among muscle fibers and an intense reaction in endothelia of blood vessels were noted. Strong immunostaining appeared inside vacuoles of vacuolar degeneration changes of muscle fibers, and in regenerating muscle fibers in PM and DM. No macrophages were found next to the CD59 positive muscle regions. The results seem to strongly support a role of the complement (C) system and of the factors protecting cells from the C-induced damage in the mechanism of muscle injury in PM and DM. The findings can have treatment implications.

The effects of histamine injection on the histochemistry of the guinea pig parathyroid gland.

Histochemical studies on the activity of some neuropeptides (PGP, CT, NPY, SP and betaE) and enzymes (AP, AlP, SDH and MAO) were performed on guinea pig parathyroid glands after injections of histamine, histamine receptor blockers and muscarinic receptor blocker. Under conditions of histamine shock, the immunoreactivity of CT and the reactivity of SDH and MAO were found to decrease together with an increase in the activity of betaE and AP. The reactions for SP, NPY, PGP and AlP did not change in any of the groups.

Histological pictures of muscles and an evaluation of cellular infiltrations in human polymyositis/dermatomyositis, as compared to the findings in experimental Guinea pig myositis.

We tested whether intramuscular injections of dermatomyositis (DM) patients' sera into guinea pig muscles can be used to transfer myositic alterations to these animals. Additionally, similar tests were performed using neoplastic patients' sera and sera from non-neoplastic, non-myositic patients. The DM patients' sera induced idiopathic inflammatory myopathy (IIM) type histological changes in muscle fibres in guinea pig quadriceps muscles, which were especially evident 72 h after sera injections. Immunohistochemical stainings of myositic guinea pig muscles were done for guinea pig pan-T-cells, monocytes/macrophages, the neuronal marker-protein gene product 9.5 (PGP 9.5) and protein S-100. Our studies proved that the factor(s) responsible for the appearance of characteristic alterations in diseased muscles during the course of DM is/are present in patient sera.

A morphological and immunohistochemical investigation of guinea pig skin after the introduction of substance P and VIP.

The aim of this study was to examine a morphological picture of guinea pig skin that had been injected with neuropeptides (NPS)(2)- substance P (SP) and guinea pig vasoactive intestinal peptide (VIP) - to elucidate their local influence. Routine histological stainings were performed, together with immunohistochemical reactions for T cells and for macrophages. In the deeper layers of the skin, T cell and macrophagic infiltrations were observed. The intensity of these changes was greater 24 hours after injections than that observed at the third hour of the experiment.

Effect of intramuscular application of selected neuropeptides on morphology of muscle.

The aim of the study was to examine a morphological picture of guinea pig skeletal muscles injected with neuropeptide Y (NPY), substance P (SP) or vasoactive intestinal peptide (VIP), to evaluate the influence of a single injection of the mentioned neuropeptides (NPS) on muscle morphology and mast cell, T lymphocyte and macrophage chemotaxis. There were different degrees of muscle fibre injuries as well as different intensities and compositions of infiltrations inside the muscle after the introduction of the NPS. The observed changes did not disappear, but increased after 24 hours, comparing to the 3-hour post-injection changes, suggesting that NPS are proinflammatory rather than antiinflammatory factors in skeletal muscles. The local, particularly delayed action of NPS in vivo requires further studies.