MONOCYTE CHEMOTACTIC PROTEIN-1 IS A PROINFLAMMATORY CHEMOKINE IN RAT SKIN INJECTION SITES AND CHEMOATTRACTS BASOPHILIC GRANULAR CELLS

Chemokines may control mast cell infiltrates found in many inflammator y diseases, These cells act through at least two main functions: migra tion and degranulation, Here we show that human recombinant monocyte c hemotactic protein (MCP)-1 (10 ng/50 mu l) induces, after 4 h, an infl ammatory vascular permeability and cellular extravasation reaction, de termined by Evan's blue dye (1% in saline) injected into the tail vein of the rat, when injected intradermally in the rat skin. The blue col or accumulating at the sites of injection provides evidence of vascula r permeability and cellular extravasation. The colored areas of the sk in were then enucleated and immersed in a fixative solution, Slides we re prepared with sections of tissue colored with toluidine blue and an alyzed under an optical microscope. A significant number of basophilic cells migrated to the injected area where MCP-1 (10 ng/50 mu l) was u sed compared to the control PBS treatment. Cell recruitment was slight ly less than N-formyl-methionine-leucyl-phenylalanine (used at 10(-6) M/50 mu l). Electron microscopy studies confirmed the presence of baso philic granular cells where MCP-1 was intradermally injected. After pr eparation of a histidine decarboxylase (HDC) probe, a Northern blot an alysis was determined for HDC mRNA in the enucleated tissue injected w ith MCP-1 (10 ng/50 mu l). Steady-state levels of HDC mRNA levels were induced after 4 h, These results were confirmed by the higher amount of histamine release, compared to the control PBS, in the enucleated t issue from the MCP-1 injection sites. Our results suggest that MCP-1 c ould play a significant role in diseases characterized by basophilic c ell accumulation and migration to sites of tissue damage. Moreover, we show for the first time that MCP-1 is a pro-inflammatory chemokine th at induces basophilic cell migration in rat skin injection sites.