In a steady state, elevated number of CD14++ CD16+ PBMs can be ex

In a steady state, elevated number of CD14++ CD16+ PBMs can be explained by relatively less trafficking of CD14++ CD16+ than CD14++ CD16− cells into inflammatory tissues. In stable asthmatic patients, we found decreased expression of CD16 on bronchial

macrophages, which may reflect preferential influx of CD16− PBMs into the airways in asthmatics as compared to non-asthmatic subjects [28]. However, during acute asthma attack such as that seen after allergen exposure, preferential sequestration of CD14++ CD16+ PBMs may occur. It has been demonstrated that acute skin injury results in preferential accumulation of CD16+ monocytes [29]. Chemokines are crucial in directing individual cell migration into inflammatory sites. Surprisingly, we were not able to correlate plasma concentration of two major monocyte chemotactic chemokines CCL2 and CX3CL1 with the number of circulating monocyte subsets. Cell Cycle inhibitor However, an inverse correlation between CCL17

and the number of circulating CD14++ CD16+ monocytes 24 h after allergen challenge supports the concept of involvement of CCL17 and its receptor CCR4 in monocyte activation/migration. Among all chemokines, CCL17 and CCL22 which are ligands of the CCR4 are crucial for the attraction of cells which fuel Th-2 type immune response [30]. In fact, the key role of CCR4 in migration of T cells into airways of asthmatic patients has already been demonstrated [30]. However, the role of CCR4 in migration of monocytes has not been investigated. There is also little information concerning the expression of CCR4 on individual subsets of PBMs. Elevated expression of CCR4 on PBMs has been demonstrated in rheumatoid arthritis patients but the study did not address the expression of CCR4 on individual PBM subpopulations [31]. The CCR4-dependent activation of macrophages may play a role in inflammatory response

and tissue remodelling [32]. In an experimental model of bleomycin-induced pulmonary fibrosis, CCR4 played a crucial role in activation of pulmonary macrophages which in turn led to pulmonary fibrosis. Although in that experimental model, genetic modification leading to the absence of CCR4 did Thymidine kinase not significantly affect inflammatory cell recruitment to the lungs in response to bleomycin challenge. Interestingly, lung macrophages in the CCR4 knockout mice differed morphologically from those in the wild-type mice. Unfortunately, our study cannot prove if CCR4 selectively affects migration of some monocyte subsets or influences activation and/or maturation of monocytes. However, strong increase in plasma concentration of CCL17 and expression of CCR4 on some CD14++ CD16+ PBMs whose number decreases after allergen challenge strongly suggest a possible cause–effect relationship.

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