Regulated upon activation normal T expressed and secreted (RANTES) is a new inducible protein member of the human CC branch of chemokines. RANTES is a potent monocyte and lymphocyte chemoattractant and is a mediator of inflammatory responses. In these studies we found that RANTES 10 ng50 μl chemoattracts basophilic cells in a dose-dependent manner 4 h after an intradermal injection in rat skin sites, as revealed by optic microscopy. Moreover, in biopsy specimens from rat skin injection sites histamine release was significantly higher (P < 0.05) than in controls (PBS 50 μl) after 4 h from RANTES treatment. The presence of basophilic cells in rat skin injection sites after RANTES-treatment was also confirmed by electron microscopy studies. In addition, histidine decarboxylase (HDC) mRNA was increased in rat skin sites injected with RANTES compared to sites injected with PBS (controls). Our report describes additional biological activities for RANTES, suggesting that this human chemoattractant protein may play a fundamental role in histamine and HDC generation, along with basophilic cell recruitment.

Chemokines are a family consisting of at least ten distinct novel 8-10 kD cytokines. Monocyte chemoattractant protein-1 (MCP-1) is the prototype of the CC chemokine subfamily, purified from different sources with chemoattractant and activator properties. In this study we found that supernatants derived from TNF-alpha (10 ng/ml) or LPS (10 mu g/ml)-activated rat peritoneal mast cell cultures (5 x 10(5)/ml), incubated for 18 h, produced levels in the order of 560 and 420 pg/ml of MCP-1, respectively. This data describes an additional mode of generation of MCP-1.

Prostaglandins and thromboxanes (T×s) are produced by polymorphonuclears (PMNs) and macrophages (MØs) in response to various stimuli. PMNs were separated from other human blood cells and MOs were separated from rat peritoneal lavage. In this paper we show that human recombinant interleukin-1 (hrIL-1) can stimulate the release of thromboxane B2(T×B2) by PMNs and MØs. In addition, we have shown that aggregation of PMNs may occur when calcium ions (7 mM) and hrIL-1 (100 ng/ml) are added to the cell preparation, but not when Ca2+ alone, hrIL-1 alone, or first hrIL-1 then calcium are added to the cell preparation. The treatment of human platelets with hrIL-1 shows that after 15 min incubation T×B2 is released. In addition, we compared the aggregation of platelets caused by ADP with that caused by hrIL-1. Human recombinant IL-1 at a concentration of 100 ng/ml also causes little aggregation of platelets, in this case the aggregation is reversible. In conclusion, hrIL-1β stimulates T×B2 release in PMNs, MØs and platelets and this effect increases with addition of Ca2+ ions. The mixture of hrIL-1 and Ca2+ causes little aggregation of PMNs. In monocyte suspensions, pretreated with human recombinant IL-1 receptor antagonist (IL-Ira) 500 ng/ml for 10 min and then treated with LPS or hrIL-1β 10 μg/ml, the release of T×B2 was partially inhibited. IL-Ira may play a significant role in the control of IL-1 and LPS induction in the release of T×B2.