Lymphotactin gene expression in mast cells following Fc(epsilon) receptor I aggregation: modulation by TGF-beta, IL-4, dexamethasone, and cyclosporin A.
Recruitment of lymphocytes is a prominent feature of allergic inflammation. However, the mechanisms by which lymphocytes are attracted to such sites are not understood. Recently, cDNAs encoding a lymphocyte-specific chemokine, lymphotactin (Ltn), were isolated from mouse pro-T cell and human CD8+ T cell libraries, leading us to hypothesize that mast cells might also produce Ltn. Using the reverse transcriptase-PCR and Northern blot analysis, we found that the Ltn gene is inducible in C1.MC/C57.1 and murine bone marrow-cultured mast cells (BMCMC) by Fc(epsilon)RI aggregation. Activation of a human mast cell (HMC-1) or basophil cell line (KU812) similarly led to transcription of Ltn. Fc(epsilon)RI aggregation-dependent Ltn mRNA expression was detected by 1 to 2 h, maximal at 6 h, independent of de novo protein synthesis, and was inhibited by cyclosporin A and dexamethasone. Compared with macrophage inflammatory protein alpha (MIP-1alpha), Fc(epsilon)RI-dependent Ltn and MIP-1alpha mRNA levels were up-regulated by IL-4, but not IFN-gamma, although higher levels of IL-4 (100 and 1000 U/ml) inhibited Ltn expression only; and TGF-beta preferentially enhanced Fc(epsilon)RI-dependent Ltn mRNA levels, suggesting that Ltn and MIP-1alpha have shared and unique regulatory mechanisms. A rabbit polyclonal Ab against a synthetic peptide was developed for use in immunoblot analysis and detected a 15-kDa Ltn protein within mast cell pellets and in the supernatants of mast cells following Fc(epsilon)RI aggregation. Ltn is thus expressed in mast cells and may contribute to the recruitment of lymphocytes to areas of allergic inflammation.
Rumsaeng
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Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Vliagoftis
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Metcalfe
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D000818:Animals; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019744:Chemokines, C; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008222:Lymphokines / Q000235:genetics*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011940:Receptor Aggregation; D017455:Receptors, IgE / Q000502:physiology*; D012795:Sialoglycoproteins / Q000235:genetics*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019744:Chemokines, C; D005938:Glucocorticoids; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D017455:Receptors, IgE; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; C092390:XCL1 protein, human; C486249:Xcl1 protein, mouse; C018997:lymphotactin; D015847:Interleukin-4; D003907:Dexamethasone; D016572:Cyclosporine; D003513:Cycloheximide