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Titolo:
CHEMOTACTIC CYTOKINES AND INFLAMMATION - BIOLOGICAL PROPERTIES OF THELYMPHOCYTE AND MONOCYTE CHEMOTACTIC FACTORS ELCF, MCAF AND IL-8
Autore:
ZACHARIAE COC;
Indirizzi:
AARHUS UNIV,MARSELISBORG HOSP,DEPT DERMATOL DK-8000 AARHUS DENMARK
Titolo Testata:
Acta dermato-venereologica
, , anno: 1993, supplemento:, 181
pagine: 1 - 37
SICI:
0001-5555(1993):<1:CCAI-B>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; NEUTROPHIL-ACTIVATING PEPTIDE; HUMAN-ENDOTHELIAL-CELLS; HUMAN DERMAL FIBROBLASTS; PLATELET BASIC-PROTEIN; NATURAL-KILLER CELLS; MEMORY T-CELLS; DELAYED-TYPE HYPERSENSITIVITY; BLOOD MONONUCLEAR LEUKOCYTES; HUMAN INTERLEUKIN-8 RECEPTOR;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
312
Recensione:
Indirizzi per estratti:
Citazione:
C.O.C. Zachariae, "CHEMOTACTIC CYTOKINES AND INFLAMMATION - BIOLOGICAL PROPERTIES OF THELYMPHOCYTE AND MONOCYTE CHEMOTACTIC FACTORS ELCF, MCAF AND IL-8", Acta dermato-venereologica, 1993, pp. 1-37

Abstract

This thesis discusses the phenotypic characteristics of different inflammatory dermatological diseases and sets this into context with the specific chemotactic ability of different cytokines. It further discusses the biological properties of different chemotactic cytokines and their relevance in certain inflammatory diseases. The term chemotaxis was introduced in 1884 by Pfeffer, who described it as directional migration of leukocytes along a gradient. Regular studies of chemotaxis were, however, not possible until 1962 when Boyden developed the chemotaxis chamber technique. This test has since then been improved, and it is now possible to define and characterize chemoattractants and examine the special chemotactic behavior of leukocytes. We investigated T lymphocyte responses towards different chemoattractants using a modifiedBoyden chamber technique and found that approximately 50% of normal individuals have cells which respond whereas T-cells from the remainingpersons did not respond. We therefore chose human T lymphocytic cell lines as target cells for chemotaxis screening to avoid inter-individual variations among donors. T lymphocytic infiltrates dominated by CD4, CD45R0+ memory T cells are characteristic for many dermatological inflammatory diseases. We have therefore performed experiments to evaluate whether an earlier described epidermal lymphocyte chemotactic factor (ELCF) from skin overlying a tuberculin skin reaction in addition with other cytokines specifically attracts different subsets of lymphocytes. ELCF which probably reflects a mixture of different epidermal T lymphocyte chemotactic factors rather than a single factor was shown to specifically attract CD4+, CD45R0+ T lymphocytes in contrast to fMLP, IL-8, C5a and LTB4, which induced equal chemotaxis for both CD4+ andCD8+ T lymphocytes. A newly described inhibitory cytokine IL-10 selectively attracted the CD8+ subpopulation of T lymphocytes, and it is suggested that IL-10 could be an important factor in the downregulation of an inflammatory response. The recently discovered neutrophil chemotactic and activating factor IL-8 has been shown to be chemotactic for T lymphocytes as well. It belongs to a family of 8,000 - 10,000 KDa peptides of which a monocyte chemotactic and activating factor MCAF is also a member. We showed that mRNA for IL-8 could be expressed in highly purified T lymphocytes only upon stimulation with ionomycin and PHA or PMA and PHA, and to a lesser extent PMA and IL-2. This is consistent with other reports of T lymphocytes requiring two signals for cytokine production. We showed that it was only the CD4+ subpopulation of the T lymphocytes that expressed IL-8 mRNA. Experiments with the combination of fixed numbers of T lymphocytes and monocytes revealed that it is unlikely that the production of IL-8 is dependent on the accessory function of the monocytes. Only very small amounts of IL-8 protein were detected in the supernatants of the stimulated T lymphocytes, so through immunoprecipitation experiments of cell lysates it is suggested that the IL-8 production was inhibited at a posttranscriptional level. We further showed that large granular lymphocytes (LGL) were able to express mRNA for IL-8 and secrete the protein upon stimulation with PHAin the presence of IL-2 or PMA, PMA alone or in the combination with ionomycin. Anti-CD16 mAb stimulated LGL to express mRNA for IL-8. MCAFwas purified from supernatants of a TNFalpha stimulated fibrosarcoma cell line. MCAF selectively attracts monocytes and stimulates superoxide anion and N-acetyl beta-glucosaminidase releasing activity in humanmonocytes. In addition, although not directly inhibitory to tumor growth, MCAF was shown to activate monocytes to augment cytostatic activity towards several tumor cell lines. Further we injected MCAF subcutaneously into the ears of Lewis rats and saw a predominant monocytic infiltrate after 18 hours. Using receptor competition assays we established that the receptors for MCAF were distinct from the IL-8-receptors. As MCAF possesses strong monocyte activating activities as well as monocyte cytostatic augmenting activity it was speculated whether MCAF plays a role in tumor growth control by attracting and activating macrophages at tumor site. MCAF probably plays a role in atherosclerosis anddelayed hypersensitivity. Human melanocytes were shown to express mRNA for IL-8 and MCAF as well as to secrete the proteins upon stimulation with either IL-1 or TNFalpha. This suggests a possible role for melanocytes during an immunological inflammatory reaction. In contrast different melanoma cell lines could only be stimulated to express mRNA for IL-8 and not MCAF. This discrepancy between the melanocytes and melanoma cell lines in their ability to secrete MCAF may be important for the understanding of the development of malignant metastazing melanomas. Monosodium urate crystals stimulated human monocytes to release a neutrophil chemotactic and activating factor. This factor was shown to be identical with IL-8. Additionally IL-8 was significantly increased in gouty synovial fluids relative to osteoarthritic synovial fluids. Microcrystal-induced secretion of IL-8 plays a possible role in a number of crystal-induced inflammatory conditions. It was concluded that different epidermal leukocyte chemotactic factors may play an important role during inflammatory skin reactions by attracting and activating asequence of different leukocytes, which might be specific for the inflammatory condition.

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Documento generato il 30/10/20 alle ore 00:29:18