FORMATION OF EOSINOPHILIC AND MONOCYTIC INTRADERMAL INFLAMMATORY SITES IN THE DOG BY INJECTION OF HUMAN RANTES BUT NOT HUMAN MONOCYTE CHEMOATTRACTANT PROTEIN-1, HUMAN MACROPHAGE INFLAMMATORY PROTEIN 1-ALPHA, OR HUMAN INTERLEUKIN-8

Equilibrium binding studies on canine mononuclear and granulocytic cel ls allow the identification of a single high affinity receptor for the human C-C chemokine RANTES (dissociation constant, 14 +/- 8 pM), that , in contrast to the human RANTES receptor, has no affinity for human macrophage inflammatory protein 1alpha (hMIP-1alpha). A single intrade rmal injection of hRANTES in dog resulted in eosinophil- and macrophag e-rich inflammatory sites within 4 h. Cell infiltration peaked at 16-2 4 h after hRANTES injection. There was histological evidence of intrav ascular activation of eosinophils at 4 h, although eosinophils in the vasculature and interstitium contained apparently intact granules. Mon ocytes were the predominant cells adherent to venular endothelium at 1 6-24 h. Human MIP-1alpha elicited no response in canine dermis, wherea s monocyte chemoattractant protein 1 caused mild perivascular cuffing with monocytes. In contrast, human interleukin 8 induced a neutrophili c dermal infiltrate that was maximal by 4 h after challenge. This prov ides the first direct evidence in vivo that RANTES has significant pro inflammatory activity and, in addition, could be a mediator in atopic pathologies characterized by eosinophilic and monocytic inflammatory r esponses.