TNF-alpha renders human neutrophils responsive to platelet factor 4. Comparison of PF-4 and IL-8 reveals different activity profiles of the two chemokines
| Autor: | F Petersen, A Ludwig, H D Flad, E Brandt |
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| Rok vydání: | 1996 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 156:1954-1962 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.156.5.1954 |
| Popis: | Platelet factor 4 (PF-4), like IL-8, is a member of the chemokine superfamily of proinflammatory cytokines. However, although the capacity of IL-8 to stimulate functions in neutrophils is well established, reports on PF-4 are still contradictory. In the present study, we have prepared highly purified PF-4 and examined its ability to induce chemotaxis, degranulation, adhesion to gelatin and plasma proteins, and changes in intracellular calcium levels. Even over a broad range of concentrations, PF-4 alone was unable to induce functional changes in PMN. However, neutrophils pre- or co-incubated with physiologically relevant concentrations of TNF-alpha responded to PF-4 by the selective mobilization of the secondary granule marker lactoferrin but not of the primary granule marker elastase. Contrary to IL-8, PMN did not require pretreatment with cytochalasin B for PF-4-induced exocytosis of lactoferrin. The synergistic effect of PF-4 with TNF-alpha was not a priming phenomenon because the cooperative response remained unchanged even when TNF-alpha was added 5 min after the chemokine. In contrast, TNF-alpha-treated PMN did not respond to PF-4 by chemotaxis or by an increase of intracellular calcium levels, and no competition of PF-4 for IL-8 receptors was observed. Our results suggest a mechanism as well as a biologic role of PF-4 in the regulation of neutrophil function, which is different from that of IL-8 and other alpha-chemokines. |
| Databáze: | OpenAIRE |
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