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CCL2 KO mice demonstrate enhanced TH2 responses following dermal sensitization.

Myers-LP; Simeonova-P; Meade-BJ
Toxicologist 2005 Mar; 84(Suppl 1):349
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 & 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 & 47.4, respectively), as well as a slight increase in proliferation to HCA (7.5 & 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.
Laboratory-animals; Animals; Animal-studies; Sensitization; Exposure-levels; Exposure-assessment; Lymph-nodes; Skin-exposure; Skin-sensitivity
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Fiscal Year
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NIOSH Division
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana