The signal transduction pathway involved in the migration induced by a monocyte chemotactic cytokine

Silvano Sozzani, Walter Luini, Marina Molino, Petr Jílek, Barbara Bottazzi, Chiara Cerletti, Kouji Matsushima, Alberto Mantovani

Research output: Contribution to journalArticle

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 (2+ 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.

Original languageEnglish
Pages (from-to)2215-2221
Number of pages7
JournalJournal of Immunology
Volume147
Issue number7
Publication statusPublished - Oct 1 1991

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polycarbonate
Chemotaxis
Chemokines
Protein Kinase C
Monocytes
Signal Transduction
Phosphotransferases
Guanylate Kinases
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Bordetella pertussis
Collodion
Staurosporine
Fura-2
Chemokine CCL2
Protein-Serine-Threonine Kinases
Pertussis Toxin
Myosins
Ion Channels
Protein Kinases
Neutrophils

ASJC Scopus subject areas

  • Immunology

Cite this

The signal transduction pathway involved in the migration induced by a monocyte chemotactic cytokine. / Sozzani, Silvano; Luini, Walter; Molino, Marina; Jílek, Petr; Bottazzi, Barbara; Cerletti, Chiara; Matsushima, Kouji; Mantovani, Alberto.

In: Journal of Immunology, Vol. 147, No. 7, 01.10.1991, p. 2215-2221.

Research output: Contribution to journalArticle

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