RANTES IS A PRO-INFLAMMATORY CHEMOKINE AND CHEMOATTRACTS BASOPHIL CELLS TO EXTRAVASCULAR SITES

RANTES (regulated upon activation normal T expressed and secreted) is another member of the intercrine beta subfamily which acts as a select ive chemoattractant for human monocytes and CD4-positive lymphocytes a nd increases the adherence of monocytes to endothelial cells, In this work, the effect of RANTES was studied on sat skin injection sites, Ra ts were intradermally injected with 50 mu l of RANTES, at different co ncentrations, fMet-Leu-Phe (FMLP), or LPS (Positive controls) or PBS v ehicle (negative control). The animals were then injected with 0.6 ml of Evens' blue in the tail vein in order to obtain a blue colour in th e areas where the compounds were injected. After 4 h the rats were kil led and the maximum diameter of the blue extravasation area was measur ed, The coloured areas were then excised and optical and electron micr oscopic studies were performed, in addition, in some of the excised ti ssue, a Northern blot analysis for histidine decarboxylase (HDC) mRNA was performed along with an estimation of the amount of histamine gene rated in the tissue injection sites, In these studies it was found tha t intradermal injections of 5, 2.5, and 1.25 x 10(-5) M RANTES produce d a strong inflammatory response with the accumulation of a great numb er of basophil cells compared with the PBS (50 mu l) negative control, or FMLP (10(-6) M/50 mu l) or LPS (10 ng/50 mu l) positive control, a fter 4 h. Moreover, 5, 2.5, 1.25 x 10(-5) M RANTES produced a dose-res ponse stimulation of HDC mRNA in the tissues of skin injection sites. The increasing number of basophils in the RANTES inflamed tissues led to augmentation of histamine content, compared with the PBS control. I n conclusion, the pro-inflammatory chemokine RANTES stimulates the gen eration of HDC mRNA in skin injection sites. (C) 1997 John Wiley & Son s, Ltd.