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| THE SIGNAL TRANSDUCTION PATHWAY INVOLVED IN THE MIGRATION INDUCED BY A MONOCYTE CHEMOTACTIC CYTOKINE |
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| Author(s): SOZZANI S, LUINI W, MOLINO M, JILEK P, BOTTAZZI B, CERLETTI C, MATSUSHIMA K, MANTOVANI A |
| Source: JOURNAL OF IMMUNOLOGY Volume: 147 Issue: 7 Pages: 2215-2221 Published: OCT 1 1991 |
| Times Cited: 151 References: 42 |
| Abstract: Recombinant monocyte-chemotactic and activating factor (rMCAF; alternative acronyms MCP-1, TDCF, human JE) induced migration of human monocytes across polycarbonate or nitrocellulose filters. Maximal induction of migration was observed at a concentration of 10 ng/ml (10(-9) M). Checkerboard analysis revealed that rMCAF elicited true gradient-dependent chemotactic migration, although a gradient independent chemokinetic effect was observed at low concentrations (1-5 ng/ml). rMCAF caused a rapid (< 5 s) and transient (approximately 1.5 min) increase of free cytosolic Ca2+ ions, as assessed by the fura-2 probe. No Ca2+ increase was detected in neutrophils or lymphocytes stimulated by rMCAF. Studies conducted in the absence of extracellular Ca2+ or in the presence of Ni2+ (an inhibitor of Ca2+ influx) suggested that the increase of intracellular Ca2+ induced by rMCAF is dependent on the influx of extracellular Ca2+ through plasma membrane channels. Bordetella pertussis toxin inhibited the intracellular Ca2+ elevation and chemotaxis caused by rMCAF. The possible involvement of Ca2+-dependent protein kinases in rMCAF signaling pathway(s) was explored using inhibitors. Inhibitors of GMP-dependent kinase and myosin L chain kinase had no effect on rMCAF-induced monocyte migration. In contrast, protein kinase C/cAMP-dependent kinase inhibitors (such as, C-I, H-7, HA-1004, KT5720, and Staurosporine) markedly decreased rMCAF induced chemotaxis suggesting the involvement of a serine/threonine protein kinase, possibly protein kinase C, in rMCAF signaling pathway. |
| Document Type: Article |
| Language: English |
Addresses:
1. MARIO NEGRI INST PHARMACOL RES, VIA ERITREA 62, I-20157 MILAN, ITALY
2. IST RIC FARMACOL MARIO NEGRI, CONSORZIO MARIO NEGRI SUD, I-66030 SANTA MARIA IMBARO, ITALY
3. KANAZAWA UNIV, CANC RES INST, DEPT PHARMACOL, KANAZAWA, ISHIKAWA 920 JAPAN |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Immunology |
| IDS Number: GH524 |
| ISSN: 0022-1767 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |