Chemotaxis of different populations of cells and release of proinflammatory mediators in response to antigenic stimulation are important processes in allergic diseases. These lead to the late phase response, a hallmark of chronic allergic diseases. Recombinant RANTES, a member of the "intercrine/ chemokine" family of cytokines, has been previously shown to be chemotactic for monocytes and T cells of memory/helper phenotype. In this manuscript, we show that it is capable of inducing histamine release from human basophils at concentrations as low as 10-10 M and compare its activity with that of monocyte chemotactic and activating factor/ monocyte chemoattractant protein-1 (MCAF/MCP-1), another intercrine/chemokine. RANTES (10-7 M) caused histamine release from the leukocytes of 26 of 33 donors tested (mean 21.8 ± 3.1%). In the same group of donors, MCAF/MCP-1, goat anti-human IgE (anti-IgE; 1 μg/ml), and FMLP (10-5 M) released 41.1 ± 2.9%, 40.5 ± 4.6%, and 44 ± 3.1% histamine, respectively. The percent histamine release by RANTES in atopic vs nonatopics was 30.3 ± 6.7 and 16.5 ± 2.4, respectively (p <0.05), and histamine release by RANTES correlated significantly with histamine release by MCAF (r = 0.69; p <0.001) but not with histamine release by anti-IgE (r = 0.29; p > 0.05). Histamine release by RANTES and MCAF/ MCP-1 was extremely rapid, reaching a maximum within 1 min. RANTES was also shown to activate highly purified basophils (80% pure), and its activity was inhibited by a polyclonal anti-RANTES antibody. At a suboptimal concentration (6 × 10-9 M), RANTES did not prime basophils to enhance histamine release by secretagogues such as anti-IgE, C5a, or FMLP. On the other hand, preincubation of basophils with RANTES or MCAF/MCP-1 desensitized basophils to either factor but not to anti-IgE, C5a, or FMLP. Preincubation of basophils with pertussis toxin markedly diminished the basophil response to either RANTES or MCAF/MCP-1. These results suggest that RANTES and MCAF/MCP-1: 1) are potent activators of basophils; 2) may function via the same, or a closely related, receptor system in basophils; and 3) may represent a link between activation of monocytes, lymphocytes, and basophils in inflammatory disorders such as the late phase allergic reaction.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Immunology|
|State||Published - Jul 15 1992|
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