Platelet factor 4/CXCL4 induces phagocytosis and the generation of reactive oxygen metabolites in mononuclear phagocytes independently of Gi protein activation or intracellular calcium transients

Pervushina, O; Scheuerer, B; Reiling, N; Behnke, L; Schroder, JM; Kasper, B; Brandt, E; Bulfone-Paus, S; Petersen, F

Author(s): Pervushina, O; Scheuerer, B; Reiling, N; Behnke, L; Schroder, JM; Kasper, B; Brandt, E; Bulfone-Paus, S; Petersen, F;
Details: Publication Year 2004-08-01,Volume 173,Issue #3,Page 2060-2067
Journal Title: JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: Platelet factor 4 (PF-4), a platelet-derived CXC chemokine, is known to prevent human monocytes from apoptosis and to promote differentiation of these cells into HLA-DR- macrophages. In this study, we investigated the role of PF-4 in the control of acute monocyte proinflammatory responses involved in the direct combat of microbial invaders. We show that PF-4 increases monocyte phagocytosis and provokes a strong formation of oxygen radicals but lacks a chemotactic activity in these cells. Compared with FMLP, PF-4-induced oxidative burst was later in its onset but was remarkably longer in its duration (lasting for up to 60 min). Furthermore, in PF-4-prestimulated cells, FMLP- as well as RANTES-induced burst responses became synergistically enhanced. As we could show, PF-4-mediated oxidative burst in monocytes does not involve Gi proteins, elevation of intracellular free calcium concentrations, or binding to CXCR3B, a novel PF-4 receptor recently discovered on endothelial cells. Moreover, we found that PF-4 acts on macrophages in a dual manner. On the one hand, very similar to GM-CSF or M-CSF, PF-4 treatment of monocytes generates macrophages with a high capacity for unspecific phagocytosis. On the other hand, short term priming of GM-CSF-induced human macrophages with PF-4 substantially increases their capability for particle ingestion and oxidative burst. A comparable effect was also observed in murine bone marrow-derived macrophages, indicating cross-reactivity of human PF-4 between both species. Taken together, PF-4 may play a crucial role in the induction and maintenance of an unspecific immune response.
Publisher: AMER ASSOC IMMUNOLOGISTS
Keywords: FACTOR-IV; HUMAN-NEUTROPHILS; MITOGENIC ACTIVITY; CYTOKINE RANTES; CXC CHEMOKINES; PEPTIDE-III; PLATELET-FACTOR-4; INTERLEUKIN-8; MONOCYTE; RECEPTOR
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Creation Date: 2004-08-01 12:00:00