Cattani Franca, Gallese Anatolia, Mosca Marco, Buanne Pasquale, Biordi Leda, Francavilla Sandro, Coletti Gino, Pellegrini Luigi, Melillo Gabriella, Bertini Riccardo
Research Center, Department of Preclinical Pharmacology, Dompé SpA, via Campo di Pile, 67100 L'Aquila, Italy.
Eur Cytokine Netw. 2006 Mar;17(1):42-8.
The recruitment of polymorphonuclear neutrophil leukocytes (PMN) into a challenge site, and their subsequent activation, are thought to play a role in the elicitation of the contact hypersensitivity (CHS) response. The present study investigated the role played by CXCR2 activity in tissue PMN infiltration and subsequent triggering of CHS. Our results show that the cutaneous infiltration by PMN, induced by hapten challenge was dramatically inhibited in sensitized, CXCR2-deficient (CXCR2(-/-)) mice. Inhibition of PMN recruitment into the hapten-challenged ears of CXCR2(-/-) mice was associated with a consistent reduction of the CHS response (ear swelling) in CXCR2(-/-) mice as compared with that observed in neutropenic, wild-type (CXCR2(+/+)) mice. Prevention of skin PMN infiltration and the ear swelling response by the absence of functional CXCR2 was observed regardless of the hapten used. These data clearly suggest that CXCR2 activity plays an essential role in mediating cutaneous recruitment and activation of PMN, and thus indirectly regulates recruitment of hapten-primed T cells into challenge sites, with the subsequent elicitation of the CHS response. The role played by CXCR2 activity in the CHS response provides the rationale for testing CXCR2 inhibitors as a new therapeutic approach to skin diseases.
多形核中性粒细胞（PMN）募集至激发部位及其随后的激活，被认为在接触性超敏反应（CHS）的引发中起作用。本研究调查了CXCR2活性在组织PMN浸润及随后引发CHS中所起的作用。我们的结果显示，在致敏的CXCR2缺陷（CXCR2(-/-)）小鼠中，由半抗原激发诱导的PMN皮肤浸润受到显著抑制。与在中性粒细胞减少的野生型（CXCR2(+/+)）小鼠中观察到的情况相比，CXCR2(-/-)小鼠中PMN募集至半抗原激发的耳部受到抑制，这与CHS反应（耳部肿胀）持续降低有关。无论使用何种半抗原，均可观察到功能性CXCR2缺失可防止皮肤PMN浸润及耳部肿胀反应。这些数据清楚地表明，CXCR2活性在介导皮肤PMN募集和激活中起重要作用，从而间接调节已被半抗原致敏的T细胞募集至激发部位，随后引发CHS反应。CXCR2活性在CHS反应中所起的作用为测试CXCR2抑制剂作为治疗皮肤病的新方法提供了理论依据。
