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4090245 
Journal Article 
CCL2 KO Mice Demonstrate Enhanced Th2 Responses Following Dermal Sensitization 
Myers, LP; Simeonova, P; Meade, BJ 
2005 
Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 
TOX/5001847 
84 
1-S 
English 
Host resistance studies have demonstrated the importance of CCR2 (C-C chemokine receptor 2) in Th1 responses and CCL2 (ligand of CCR2) in Th2 responses. These studies were undertaken to evaluate the role of CCR2 and CCL2 in the development of skin sensitization. To begin this evaluation, CCL2 and CCR2 knockout (KO) mice or C57BL/6 wild-type (WT) control mice were dermally exposed to 2% 2, 4-toluene diisocyanate (TDI), 30% alpha-hexylcinnamaldehyde (HCA), or vehicle (acetone). Their response to chemical exposure was evaluated using a modified LLNA (local lymph node assay), analysis of serum IgE, and phenotypic analysis of draining lymph node cells. CCR2 KO mice demonstrated a reduced stimulation index (SI) in the LLNA to 2% TDI, as compared to the WT controls (35.8 and amp; 70.6, respectively) with little difference observed in the response to HCA (SI = 4.5 for CCR2 KO and SE = 5.1 for WT mice). Serum IgE levels after 2% TDI exposure were also significantly lower in CCR2 KO (5918 ? 877 ng/ml) compared to WT (8156 ? 632 ng/ml) mice. In contrast, CCL2 KO mice demonstrated an increased SI following exposure to 2% TDI as compared to WT controls (64.8 and amp; 47.4, respectively), as well as a slight increase in proliferation to HCA (7.5 and amp; 5.2, respectively). Moreover, CCL2 KO mice had a significant increase in serum IgE levels after TDI exposure (24542 ? 5651 ng/ml) when compared to WT treated with TDI (9345 ? 2959 ng/ml). Consistent with published studies in host resistance, where CCR2 KO mice demonstrated a Th1 defect, CCR2 KO demonstrated a slight decrease in their response to HCA, a Th1 inducing chemical. In contrast to observed effects on host resistance (Th2 defect) in CCL2 KO mice, the CCL2 KO mice demonstrated an enhanced Th2 response following exposure to the dermal sensitizer, TDI.