IL-4 down-regulates anaphylatoxin receptors in monocytes and dendritic cells and impairs anaphylatoxin-induced migration in vivo

Afsaneh Soruri, Ziba Kiafard, Claudia Dettmer, Joachim Riggert, Jörg Köhl, Jörg Zwirner*

*Corresponding author for this work
    41 Citations (Scopus)

    Abstract

    Anaphylatoxins mobilize leukocytes to the sites of inflammation. In the present study we investigated the impact of GM-CSF, IL-4, and IFN-γ on anaphylatoxin receptor expression in monocytes and dendritic cells (DC). IL-4 was identified as the strongest down-regulator of the receptors for C5a and C3a in monocytes and monocyte-derived DC (MoDC). To study the impact of IL-4 on anaphylatoxin-induced chemotaxis, an in vivo migration model was established. For this purpose, human monocytes and MoDC were injected i.v. into SCID mice that at the same time received anaphylatoxins into the peritoneal cavity. A peritoneal influx of human monocytes could be demonstrated by 4 h after injections of C5a and C3a. In line with receptor down-regulation, IL-4 treatment inhibited in vivo mobilization of human monocytes and MoDC in response to C5a and C3a. In addition to its effects on human cells, IL-4 reduced C5a receptors in murine bone marrow-derived DC and impaired recruitment of labeled bone marrow-derived DC in syngeneic BALB/c mice to i.p. injected C5a. Overall, these data suggest that inhibition of a rapid anaphylatoxin-induced mobilization of monocytes and DC to inflamed tissues represents an important anti-inflammatory activity of the Th2 cytokine IL-4.

    Original languageEnglish
    JournalJournal of Immunology
    Volume170
    Issue number6
    Pages (from-to)3306-3314
    Number of pages9
    ISSN0022-1767
    DOIs
    Publication statusPublished - 15.03.2003

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