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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 mRNA levels for histidine decarboxylase
P Conti, X Pang, W Boucher, R Letourneau, M Reale, RC Barbacane, J Thibault and TC Theoharides
Immunology Division, University of Chieti School of Medicine, Italy.
RANTES and related molecules, constitute the C-C class of chemokine
supergene family and a group of cytokines produced by hematopoietic cells
constitute the MCP-1 or C-X-C class. The roles of most of these chemokines
are not well known, although members of the C-X-C family are inflammatory
agents. Here, we report that intradermal injection of RANTES 10 ng/50
microL subcutaneously in the abdominal skin produced a strong inflammatory
reaction, as evidenced by Evans blue dye, greater than FMLP (10(-6) mol/L)
(approximately 57%); while MCP-1, 10 ng/50 microL was less effective than
FMLP (10(-6) mol/L) (approximately 54%). Moreover, the histologic analysis
of the cells stained with Toluidine blue (0.1%) were analyzed at a
magnification of x40). RANTES 10 ng/50 microL and LPS produced higher
numbers (142 +/- 11 and 193 +/- 21 of cells/200 mm2, respectively) of
basophilic cell accumulation in the skin injection sites compared with FMLP
(10(-6) mol/L) (127 +/- 14/200 mm2), while MCP-1 10 ng/50 microL was less
effective (88 +/- 10/200 mm2). Electron microscopy (x13,800) studies of
skin injection sites revealed that RANTES was chemoattractant for mast
cells. In a Northern blot analysis from homogeneous tissue biopsy from the
intradermal injection sites, RANTES was more potent than MCP-1 in
increasing histidine decarboxylase (HDC) mRNA, the sole enzyme responsible
for the production of histamine from histidine. Since PGD2 is formed by
mast cells on cell activation, we also studied the effect of RANTES and
MCP- 1 on PGD2 production in inflamed tissue in vivo. RANTES (20, 10, and 5
ng) and MCP-1 (20, 10, and 5 ng) strongly stimulated PGD2, in a dose-
dependent manner, with a potency rank order of RANTES (10 ng/mL)
approximately two times greater than MCP-1 (10 ng/mL).
Volume 89,
Issue 11,
pp. 4120-4127,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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