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 MESSENGER-RNA LEVELS FOR HISTIDINE-DECARBOXYLASE

RANTES and related molecules, constitute the C-C class of chemokine su pergene family and a group of cytokines produced by hematopoietic cell s constitute the MCP-1 or C-X-C class. The roles of most of these chem okines are not well known, although members of the C-X-C family are in flammatory agents. Here, we report that intradermal injection of RANTE S 10 ng/50 mu L subcutaneously in the abdominal skin produced a strong inflammatory reaction, as evidenced by Evans blue dye, greater than F MLP (10(-6) mol/L) (similar to 57%); while MCP-1, 10 ng/50 mu L was le ss effective than FMLP (10(-6) mol/L) (similar to 54%). Moreover, the histologic analysis of the cells stained with Toluidine blue (0.1%) we re 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 s ites compared with FMLP (10(-6) mol/L) (127 +/- 14/200 mm(2)), while M CP-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 RA NTES was chemoattractant for mast cells. In a Northern blot analysis f rom homogeneous tissue biopsy from the intradermal injection sites, RA NTES was more potent than MCP-1 in increasing histidine decarboxylase (HDC) mRNA, the sole enzyme responsible for the production of histamin e from histidine. Since PGD(2) is formed by mast cells on cell activat ion, we also studied the effect of RANTES and MCP-1 on PGD(2) producti on 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 tim es greater than MCP-1 (10 ng/mL). (C) 1997 by The American Society of Hematology.