Impact of Rantes and MCP-1 chemokines on in vivo basophilic cell recruitment in rat skin injection model and their role in modifying the protein and mRNA levels for histidine decarboxylase

RANTES and related molecules, constitute the C-C class of chemokine supergene family and a group of cytokines produced by hematopoietic cells constitute the MCP-1 or C-X-C class. The roles of most of these chemokines are not well known, although members of the C-X-C family are inflammatory agents. Here, we report that intradermal injection of RANTES 10 ng/50 mu L subcutaneously in the abdominal skin produced a strong inflammatory reaction, as evidenced by Evans blue dye, greater than FMLP (10(-6) mol/L) (similar to 57%); while MCP-1, 10 ng/50 mu L was less effective than FMLP (10(-6) mol/L) (similar to 54%). Moreover, the histologic analysis of the cells stained with Toluidine blue (0.1%) were analyzed at a magnification of x 40). RANTES 10 ng/50 mu L and LPS produced higher numbers (142 +/- 11 and 193 +/- 21 of cells/200 mm(2), respectively) of basophilic cell accumulation in the skin injection sites compared with FMLP (10(-6) mol/L) (127 +/- 14/200 mm(2)), while MCP-1 10 ng/50 mu L was less effective (88 +/- 10/200 mm(2)). Electron microscopy (x 13,800) studies of skin injection sites revealed that RANTES was chemoattractant for mast cells. In a Northern blot analysis from homogeneous tissue biopsy from the intradermal injection sites, RANTES was more potent than MCP-1 in increasing histidine decarboxylase (HDC) mRNA, the sole enzyme responsible for the production of histamine from histidine. Since PGD(2) is formed by mast cells on cell activation, we also studied the effect of RANTES and MCP-1 on PGD(2) production in inflamed tissue in vivo. RANTES (20, 10, and 5 ng) and MCP-1 (20, 10, and 5 ng) strongly stimulated PGD(2), in a dose-dependent manner, with a potency rank order of RANTES (10 ng/mL) approximately two times greater than MCP-1 (10 ng/mL). (C) 1997 by The American Society of Hematology.