The Ames Salmonella/mammalian-microsome assay was used to evaluate the bacterial mutagenicity of 6 bioactive peptides and of 11 chemical reagents used in peptide synthesis. Samples of 2 reagents, bis(2-oxo-3-oxazolidinyl)phosphinic chloride and fluoren-9-ylmethyl chloroformate, showed mutagenic activity with strains TA100 and TA1535, and with TA1537, respectively. No mutagenic activity was found with the bioactive peptides or with the other 9 peptide synthesis reagents.

Animals↗

PubMedDate not supplied

Interleukin-3 interleukin-5, and granulocyte-macrophage colony-stimulating factor expression in nasal polyps.

PURPOSE: Nasal polyps (NP) are grape-like clusters of chronically inflamed tissue. Little is known about the underlying cells and cytokines involved in nasal polyposis. For the present study, we hypothesize that elevated tissue levels of interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony-stimulation factor (GM-CSF) contribute to eosinophil recruitment and activation in NP. MATERIALS AND METHODS: To begin to test this hypothesis, we evaluated IL-3, IL-5, and GM-CSF levels and distributions in nasal polyp specimens obtained intraoperatively from 13 patients and two normal controls. For these studies, nasal polyp levels were determined by enzyme-linked immunosorbent assay (ELISA), and IL-3, IL-5, and GM-CSF distribution was determined by immunohistochemistry. RESULTS: Immunohistochemical staining of the NP indicated that in all 13 patient samples, IL-3, IL-5, and GM-CSF were associated with infiltrating cells, primarily eosinophils, in the NP. Quantitation of IL-3, IL-5, and GM-CSF in NP tissue homogenates indicated that IL-3, IL-5, and GM-CSF levels were evaluated in the NP tissues when compared with control tissues. Additionally, elevation of individual cytokines correlated with previous polypectomy (IL-3), steroid use (IL-3, IL-5, and GM-CSF), asthma (IL-5), and age (GM-CSF). CONCLUSION: These data support our hypothesis that IL-3, IL-5, and GM-CSF are likely to play a key role in eosinophil recruitment/activation and NP formation and support recently advanced theories that cytokines play a key role in the pathogenesis of this disease.

Adult↗

PubMedDate not supplied

Eosinophil expression of transforming growth factor-beta and its receptors in nasal polyposis: role of the cytokines in this disease process.

PURPOSE: Nasal polyposis (NP) is characterized by an increase in inflammatory processes including fibrosis. Because transforming growth factor beta (TGF-beta) has been proven to induce fibrosis, we hypothesize that TGF-beta and its receptors are present in NP and influence polyp development. MATERIALS AND METHODS: To test this hypothesis, we evaluated distribution (immunohistochemistry) of TGF-beta isoforms (TGF-beta 1, TGF-beta 2, and TGF-beta 3) and its receptors [(TGF-beta(RI) & TGF-beta(RII)] in NP from 36 NP patients and in five normal sinus tissue specimens obtained from septoplasty/inferior turbinectomy. Tissue levels of TGF-beta 1 and TGF-beta 2 levels were determined by enzyme-linked immunosorbent assay (ELISA) and protein content was determined by Bio Rad assay (Bio Rad, Richmond, CA). All tissue levels of TGF-beta were normalized and expressed as pg of TGF-beta per mg of total protein (pg/mg TP). RESULTS: Immunohistochemical studies showed eosinophils as the major cells positively staining for TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-beta(RI), and TGF-beta. In fibrotic sections, increased staining of eosinophils, fibroblast, and mononuclear cells was found for all three isoforms and both receptors. Evaluation of tissue levels indicated mean levels of TGF-beta 1 in the NP were 11.64 +/- 22.12 pg/mg TP versus normal control mean 44.36 +/- 22.12 pg/mg TP.TGF-beta 2 mean levels were 11.46 +/- 23.73 pg/mg TP versus normal control mean of 2.03 +/- 1.13 pg/mg TP. NP showed decreased expression of TGF-beta 1 and enhanced expression of TGF-beta 2 isoforms with presence of their receptors. Higher levels of TGF-beta 2 correlated with an increase in previous polypectomies perhaps indicative of severity of disease (P < or = .0001). CONCLUSION: Our studies show the presence of the TGF-beta isoforms and receptors in NP tissue. The results support our hypothesis that the eosinophil continues to be a pivotal inflammatory cell in NP, a differential regulation may govern the activity of TGF-beta in NP, and hence, the TGF-beta family of cytokines and receptors likely play a key role in controlling NP formation.

Adult↗