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 cells 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 1 alpha (hMIP-1 alpha). A single intradermal injection of hRANTES in dog resulted in eosinophil- and macrophage-rich inflammatory sites within 4 h. Cell infiltration peaked at 16-24 h after hRANTES injection. There was histological evidence of intravascular activation of eosinophils at 4 h, although eosinophils in the vasculature and interstitium contained apparently intact granules. Monocytes were the predominant cells adherent to venular endothelium at 16-24 h. Human MIP-1 alpha elicited no response in canine dermis, whereas monocyte chemoattractant protein 1 caused mild perivascular cuffing with monocytes. In contrast, human interleukin 8 induced a neutrophilic dermal infiltrate that was maximal by 4 h after challenge. This provides the first direct evidence in vivo that RANTES has significant proinflammatory activity and, in addition, could be a mediator in atopic pathologies characterized by eosinophilic and monocytic inflammatory responses.
Meurer
R
R
Department of Biochemical and Molecular Pathology, Merck Research Laboratories, Rahway, New Jersey 07065.
Van Riper
G
G
Feeney
W
W
Cunningham
P
P
Hora
D
D
Springer
M S
MS
MacIntyre
D E
DE
Rosen
H
H
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced*; D016209:Interleukin-8 / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins; D009000:Monocytes / Q000276:immunology*; D015846:Monokines / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology; D013045:Species Specificity
D023181:Antimicrobial Cationic Peptides; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines; D016209:Interleukin-8; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011506:Proteins; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic