Background Increased lung macrophage numbers in COPD may arise from upregulation

Background Increased lung macrophage numbers in COPD may arise from upregulation of blood monocyte recruitment into the lungs. macrophages was reduced in COPD compared to NS. All alveolar macrophages from COPD and S expressed the anti-apoptosis marker BCL2; this protein was not present in non-smokers or COPD ex-smokers. Conclusion COPD monocytes show decreased migratory ability despite increased CCR5 expression. Increased COPD lung macrophage numbers may be due to delayed apoptosis. Electronic supplementary material The online version of this article (doi:10.1186/s12931-017-0569-y) contains supplementary material, which is available to authorized users. Keywords: COPD, Monocytes, CCR5, Chemotaxis, Interleukin-6 Background Monocytes can be recruited from the blood buy 136236-51-6 into the tissues, whereupon differentiation into macrophages may occur [1]. There are also tissue resident macrophages that replenish cell numbers by replication [2]. A recent study demonstrated the presence of phenotypically different mononuclear phagocyte cell types in healthy human lungs that either originate from the lungs (pulmonary dendritic cells and alveolar macrophages) or from blood monocytes (monocyte derived cells and tissue monocyte/macrophages) [3]. There are increased numbers of macrophages in the lungs of chronic obstructive pulmonary disease (COPD) patients [4]; these cells are involved in host defence, airway remodelling and parenchymal destruction [5]. It has been suggested that increased lung macrophage numbers in COPD are due to increased recruitment of blood monocytes [5, 6]. Alternatively, cigarette smoke exposure induces the expression of anti-apoptotic genes in macrophages [7], and increased expression of anti-apoptotic proteins has been observed in COPD macrophages [8], suggesting that delayed apoptosis is a possible cause of macrophage accumulation in COPD. Furthermore, alveolar macrophages expressing the proliferation buy 136236-51-6 marker Ki67 have been observed in patients with interstitial lung disease [9], but whether increased macrophage accumulation in COPD occurs by self-renewal is not understood. Costa et al reported increased migration of COPD peripheral blood mononuclear cells towards C-X-C motif chemokine receptor 3 (CXCR3) and C-C motif chemokine receptor 5 (CCR5) ligands using single chemokines for migration experiments [6]. Such experiments, however do not reflect the complex mixture of chemoattractants present in the lungs [10C15]. Physiologically relevant complex supernatants, such as those obtained from induced sputum could be used to further investigate the migratory ability of COPD monocytes. CCR5 is the receptor for the monocyte chemoattractant C-C motif chemokine ligand 3 (CCL3) [16]. Studies using induced sputum and bronchoalveolar lavage have shown that CCR5 ligand levels are increased in the lungs of COPD GDF5 patients, suggesting a role for CCR5 signalling in the recruitment of monocytes into COPD lungs [12, 13, 16, 17]. Peripheral blood monocytes can be classified into 3 subtypes according to their expression of CD14 (LPS receptor) and CD16 (FcRIII receptor): CD14++CD16- (Classical), CD14+CD16+ (Intermediate) and CD14-CD16++ (Non-Classical) [1]. Increased numbers of pro-inflammatory CD14+CD16+ monocytes are buy 136236-51-6 found in chronic inflammatory disease states such as rheumatoid arthritis [18]. Furthermore, CD14+CD16+ cells have the greatest surface expression of CCR5 [1, 19]. Monocyte subsets in COPD, and their buy 136236-51-6 expression of CCR5, have not been previously reported. buy 136236-51-6 CCR5 expression is upregulated by interleukin-6 (IL-6) [20], a cytokine which trans-signals through a soluble receptor sIL-6R [21]. Plasma IL-6 levels are increased in a subset of stable COPD patients [22] and during COPD exacerbations [23]. The systemic levels of sIL-6R have not been investigated in COPD; increased systemic IL-6/sIL-6R signalling in COPD could upregulate blood monocyte CCR5 expression, thereby promoting monocyte recruitment into the lungs. We have investigated COPD blood monocyte recruitment with two major objectives.

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