Petering H, Kluthe C, Dulkys Y, Kiehl P, Ponath P D, Kapp A, Elsner J
Hannover Medical University, Department of Dermatology and Allergology, Hannover, Germany.
J Invest Dermatol. 2001 Apr;116(4):549-55. doi: 10.1046/j.1523-1747.2001.01302.x.
CC chemokine receptors are expressed on hematopoietic cells, and these may impart selective homing of monocyte, leukocyte, and lymphocyte subsets to sites of inflammation. CC chemokine receptor 3 is the major receptor on eosinophils and is also expressed on other inflammatory cells suggesting its important role for allergic diseases such as atopic dermatitis and bronchial asthma. Eotaxin, eotaxin-2 and eotaxin-3 have been identified as ligands that only activate CC chemokine receptor 3. CC chemokine receptor 3 is also activated by other promiscuous ligands, however, such as RANTES and monocyte chemotactic protein 4. To date, CC chemokine receptor 3 has not been reported to be expressed on nonhematopoietic cells. In this study, we investigated whether keratinocytes possess autocrine and paracrine mechanisms for CC chemokine secretion and receptor expression as reported for the expression of interleukin 8 and its receptors. Reverse transcriptase polymerase chain reaction analysis demonstrated that CC chemokine receptor 3 mRNA is expressed constitutively in cultured keratinocytes. The signal quantities of the CC chemokine receptor 3 amplicons showed lower intensities for keratinocytes than for eosinophils. In situ hybridization techniques exhibited that basal cell layers of the epidermis were stained homogeneously for CC chemokine receptor 3 mRNA with a decreasing signal to the upper epidermis showing that differentiating and proliferating keratinocytes did express mRNA specific for CC chemokine receptor 3. Immunohistochemical studies confirmed low expression of CC chemokine receptor 3 protein on epidermal keratinocytes compared to the high level observed on infiltrating eosinophils. Furthermore, stimulation of cultured keratinocytes with eotaxin resulted in an increased [3H]thymidine incorporation indicating a role of CC chemokine receptor 3 in epidermal proliferation and differentiation. These data demonstrate that CC chemokine receptor 3 is expressed not only on hematopoietic cells but also on keratinocytes as nonhematopoietic cells with ectodermal origin. Therefore, the identification of CC chemokine receptor 3 on epidermal keratinocytes may indicate a role for CC chemokine receptor 3 and its ligands in skin physiology and pathophysiology.
CC趋化因子受体在造血细胞上表达，这些受体可能使单核细胞、白细胞和淋巴细胞亚群选择性归巢至炎症部位。CC趋化因子受体3是嗜酸性粒细胞上的主要受体，也在其他炎症细胞上表达，提示其在特应性皮炎和支气管哮喘等过敏性疾病中发挥重要作用。嗜酸性粒细胞趋化因子、嗜酸性粒细胞趋化因子-2和嗜酸性粒细胞趋化因子-3已被确定为仅激活CC趋化因子受体3的配体。然而，CC趋化因子受体3也可被其他多效性配体激活，如RANTES和单核细胞趋化蛋白4。迄今为止，尚未报道CC趋化因子受体3在非造血细胞上表达。在本研究中，我们调查了角质形成细胞是否具有如白细胞介素8及其受体表达那样的CC趋化因子分泌和受体表达的自分泌和旁分泌机制。逆转录聚合酶链反应分析表明，CC趋化因子受体3 mRNA在培养的角质形成细胞中组成性表达。CC趋化因子受体3扩增子的信号量显示，角质形成细胞中的强度低于嗜酸性粒细胞。原位杂交技术显示，表皮的基底层CC趋化因子受体3 mRNA染色均匀，向上表皮信号逐渐减弱，表明分化和增殖的角质形成细胞确实表达CC趋化因子受体3特异性mRNA。免疫组织化学研究证实，与浸润的嗜酸性粒细胞上观察到的高水平相比，表皮角质形成细胞上CC趋化因子受体3蛋白表达较低。此外，用嗜酸性粒细胞趋化因子刺激培养的角质形成细胞导致[3H]胸苷掺入增加，表明CC趋化因子受体3在表皮增殖和分化中发挥作用。这些数据表明，CC趋化因子受体3不仅在造血细胞上表达，也在具有外胚层起源的非造血细胞角质形成细胞上表达。因此，表皮角质形成细胞上CC趋化因子受体3的鉴定可能表明CC趋化因子受体3及其配体在皮肤生理和病理生理中发挥作用。
