['94 pneumology update. Progress and perspectives in pneumology. Paradigm of change (I)].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to W Luttmann.
Explore the source record for details and available documents.
Increasing evidence has accumulated to suggest that eosinophils play a key role in the pathogenesis of asthma and other pulmonary diseases by damaging infiltrated bronchial tissue and lung parenchyma. The first part of this review on eosinophils describes the cellular characteristics and properties of the cell, which help in understanding its role in disease. The article focuses on origin, maturation and differentiation of the eosinophil, its morphological and phenotypical properties, as well as its preformed and newly generated mediators of inflammation. The cause and putative significance of eosinophil heterogeneity in respect to function and density will also be discussed. In addition, the naturally occurring mediators through which eosinophils are activated and communicate with other inflammatory cells are outlined. The first part closes with new aspects of eosinophil recruitment from the circulation into perivascular tissue, including nonselective and putative selective adhesion mechanisms and chemotaxis.
In recent years, increasing evidence has accumulated to suggest that the eosinophil represents a potent cytotoxic effector cell which plays a key role in the pathogenesis of pulmonary diseases as well as other human disorders. Beside contributing to antiparasitic host defense, eosinophils can prove detrimental to a number of host organs and tissues via release of their preformed basic proteins as well as de novo generated lipid mediators or oxygen radicals. Eosinophil effector functions are stimulated by certain lipid mediators and cytokines released by other cells in the course of active disease. In addition to their effector functions, eosinophils may have other functions in immune responses. Synthesis and expression of class II proteins of the major histocompatibility complex (MHC) may enable eosinophils to serve as antigen-presenting cells, i.e. to the antigens that appear at mucosal surfaces. In addition to collaborative interactions with lymphocytes, CD4-expressing eosinophils may elaborate cytokines that can effect cells within their tissue milieu. In conclusion, the evolving understanding of eosinophils indicates that eosinophils may not only serve as end-stage effector cells but also interact cooperatively with other cellular tissue elements in related diseases.
Endothelin (ET)-1 (10 nanoM) is about six times more effective than ET-3 in contracting the isolated iris sphincter muscle; the ET-1-induced contraction is insensitive to indomethacin treatment. The effect of ET-2 is intermediatory between ET-1 and ET-3 in contracting the muscle. The relative potency of the ETs to stimulate inositol phosphates (InsPs) in the iris-ciliary processes is ET-1 > ET-2 > ET-3, with ET-1 about six times more potent then ET-3; these effects are also insensitive to indomethacin. Studies utilizing the polymerase chain reaction (PCR) show that ETB receptors are present. Although no evidence could be found for the occurrence of ETA receptors, their presence cannot be excluded. These results suggest that the stimulation of InsPs and contraction of the iris sphincter muscle by ET is mediated by ETB receptors and that products generated via activation of phospholipase A2 are not directly involved in the observed responses. However, another type of ET receptor is indicated by the finding that ET-1 reduced the forskolin-elevated cAMP levels in the iris-ciliary epithelium. Autoradiographic results show that specific [125I]ET-1 binding sites are associated with the iris, ciliary processes and the corneal endothelium. As in the iris-ciliary process tissues, ET-1 is the most effective of the three ETs stimulating InsPs in the cornea, although statistically the differences were insignificant. Moreover, ET-1 was found to have not effect on the forskolin-elevated cAMP levels in the cornea. Whether these results reflect true differences between the ET receptors in the iris-ciliary processes and corneal endothelium remains to be established.
Recent studies have demonstrated increased levels of IL-6 in the peritoneal cavity during CAPD peritonitis. The current investigation was initiated (i) to examine the human peritoneal mesothelial cell (HPMC) as a possible source of this secreted IL-6 and (ii) to characterize the released product and examine its regulation by other cytokines. Unstimulated HPMC under growth arrested conditions released IL-6 in a time dependent manner. After 24-hour HPMC IL-6 release (mean +/- SEM, N = 13) (expressed as pg/micrograms cell protein) was 1.67 +/- 0.33. Stimulation of HPMC with IL-1 beta or TNF alpha resulted in a time (increasing up to 48 hr) and dose dependent IL-6 generation. After 24 hours the levels induced by IL-1 beta and TNF alpha (both at 1000 pg/ml) were (mean +/- SEM, N = 13) 19.08 +/- 2.98 and 6.62 +/- 1.72, respectively. Stimulation with combinations of IL-1 beta and TNF alpha resulted in additive increases in IL-6 release. This release could be inhibited by co-incubation with anti-IL-1 beta and/or anti-TNF alpha antibodies. The level of released HPMC IL-6 measured by immunometric assay (ELISA) correlated directly with that detected in the 7TD1 IL-6 bioassay (r = 0.63; P < 0.001). Western blot analysis of concentrated HPMC supernatants using specific anti-IL-6 antibody demonstrated immunoreactive bands at 23 and 28 Kd following IL-1 beta or TNF alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.