Effect of cyclosporin A on immunological response in lungs of guinea pigs infected with Trichinella spiralis.

Dzik, Jolanta M.; Zieliński, Zbigniew; Gołos, Barbara; Jagielska, Elżbieta; Wranicz, M.; Wałajtys-Rode, Elżbieta

doi:10.18388/abp.2002_3841

Cited by 8 publications

(7 citation statements)

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“…In mice showing Th1 or Th2 response, two different types of macrophage activation have been described, M-1 (classical) involving induction of iNOS and nitric oxide production and M-2 (alternative) involving arginase induction (Mosser, 2003). We have shown that T. spiralis infection of guinea pigs does not induce nitric oxide production in lung macrophages (Dzik et al, 2002a;2002b) exposed to larval antigens when newborn larvae pass to the muscles. Instead, arginase activity is enhanced in these cells (Dzik et al, 2004), concomitantly with respiratory burst induction (Dzik et al, 2006), both being elements of the non-classical type of response.…”

Section: Innate Immunity and Helminthsmentioning

confidence: 87%

Molecules released by helminth parasites involved in host colonization.

Dzik¹

2006

Acta Biochim Pol

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188

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Parasites are designed by evolution to invade the host and survive in its organism until they are ready to reproduce. Parasites release a variety of molecules that help them to penetrate the defensive barriers and avoid the immune attack of the host. In this respect, particularly interesting are enzymes and their inhibitors secreted by the parasites. Serine-, aspartic-, cysteine-, and metalloproteinases are involved in tissue invasion and extracellular protein digestion. Helminths secrete inhibitors of these enzymes (serpins, aspins, and cystatins) to inhibit proteinases, both of the host and their own. Proteinases and their inhibitors, as well as helminth homologues of cytokines and molecules containing phosphorylcholine, influence the immune response of the host biasing it towards the anti-inflammatory Th2 type. Nucleotide-metabolizing enzymes and cholinesterase are secreted by worms to reduce inflammation and expel the parasites from the gastrointestinal tract. An intracellular metazoan parasite, Trichinella spiralis, secretes, among others, protein kinases and phosphatases, endonucleases, and DNA-binding proteins, which are all thought to interfere with the host cellular signals for muscle cell differentiation. Secretion of antioxidant enzymes is believed to protect the parasite from reactive oxygen species which arise from the infection-stimulated host phagocytes. Aside from superoxide dismutase, catalase (rarely found in helminths), and glutathione peroxidase (selenium-independent, thus having a poor activity with H(2)O(2)), peroxiredoxins are probably the major H(2)O(2)-detoxifying enzymes in helminths. Secretion of antioxidant enzymes is stage-specific and there are examples of regulation of their expression by the concentration of reactive oxygen species surrounding the parasite. The majority of parasite-secreted molecules are commonly found in free-living organisms, thus parasites have only adapted them to use in their way of life.

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Section: Innate Immunity and Helminthsmentioning

confidence: 87%

Molecules released by helminth parasites involved in host colonization.

Dzik¹

2006

Acta Biochim Pol

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188

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“…Polyclonal antibodies against TGF‐β, developed against a mixture of recombinant, human TGF‐β1, porcine TGF‐β1·2, porcine TGF‐β2 and recombinant, amphibian TGF‐β5; (0·375 mg in 0·5 mL of 0·9% NaCl) were injected twice, on the 3rd and 5th days after T. spiralis infection, into the vena femoralis of anaesthetized guinea pigs. In parallel, T. spiralis ‐infected animals, used as controls, were injected with 0·9% NaCl (21). Bronchoalveolar lavage was performed on the 6th day after infection.…”

Section: Methodsmentioning

confidence: 99%

“…Cyclosporin A-treatment resulted in an attenuation of immunological response in lungs of T. spiralis-infected guinea pigs, reflected by decreased lymphocyte infiltration into the pulmonary alveolar space (21). Under those conditions CsA significantly augmented extracellular arginase activity ( Figure 2).…”

Section: Influence Of Trichinella Spiralis Infection On Guinea Pig Almentioning

confidence: 97%

“…The drug in olive oil was given per os in six doses (each dose of 20 mg / kg of body weight): 2 days and 1 day before infection with T. spiralis , and 1, 2, 3 and 4 days after infection. Animals treated only with CsA obtained placebo on the day of infection of the animals with T. spiralis (21). BAL was performed in all investigated groups on the 6th day after infection or introduction of placebo.…”

Section: Cyclosporin a Treatmentmentioning

confidence: 99%

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A non‐classical type of alveolar macrophage response to Trichinella spiralis infection

Gołos

Jagielska

et al. 2004

Parasite Immunology

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Studies of arginase expression and activity in guinea pig alveolar macrophages during Trichinella spiralis infection, prompted by earlier observation of innate lung response to the parasite, showed the macrophages to express both activity and protein of arginase type I. In cultured macrophages part of the enzyme was found to be always released to the extracellular medium. Whereas BCG in vivo treatment, alone or preceded by T. spiralis infection, stimulated arginase activity, T. spiralis infection alone affected the enzyme distribution between intracellular and extracellular fractions, and properties (K(m) and V(max)), rather than total (intracellular + extracellular) activity, with TGF-beta apparently responsible for a part of the effect. Anti-TGF-beta antibody treatment of the animals influenced both arginase activation by Mn(2+) and dependence of the enzyme-catalysed reaction on pH. Whereas T. spiralis infection activated guinea pig alveolar macrophages by the type II macrophage activation, as indicated by constant arginase expression, associated with previously demonstrated lack of stimulation of nitric oxide production, BCG treatment invoked an alternative type of activation mechanism, reflected by stimulation of macrophage arginase, but not iNOS, activity.

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“…

Cyclosporin-A(CsA) is a very potent immunosuppressive agent which is widely used in transplantations and autoimmune diseases. Recent studies suggest an encouraging clinical effect for low-dose, long-term cyclosporin A treatment in different lung diseases [1,2,3,4,5]. Whether administration of CsA might be useful for lowering the dosage of steroids during the treatment of interstitial pneumonia, asthma and lung injuries [6,7,8] is presently a matter of controversy.

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mentioning

confidence: 99%