Recruited Alveolar Macrophages, in Response to Airway Epithelial–Derived Monocyte Chemoattractant Protein 1/CCL2, Regulate Airway Inflammation and Remodeling in Allergic Asthma
Authors: John W Christman
Feng Qian
Gye Young Park
Jong Jin Jeong
Jing Deng
Yong Gyu Lee
Nizar N Jarjour
Sharmilee Nyenhuis
Sangwoon Chung
Evgeny Berdyshev
Elizabeth A B Kelly
Steven J Ackerman
Manjula Karpurapu
Viswanathan Natarajan
Ravi Ranjan
Journal: American Journal of Respiratory Cell and Molecular Biology (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MCP-1; airway epithelial cells; allergic inflammation; asthma; macrophages.
Affiliations: 1 Section of Pulmonary, Allergy, Critical Care and Sleep Medicine, the Ohio State University, Columbus, Ohio.

Abstract:  Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophage-depleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells. 

Retracted: No

PubPeer comments:
 Numerous duplications in flow cytometry. Some examples ![file] ![file] , 
 The claim is about the duplicated background of FACS data in Fig. 3 of our paper published in the AJRCMB. As we mentioned in the figure legend, Fig.3B is the further analysis of the gated population (CD163+ AMs) of Fig. 3A. Because they are the same sample, Fig. 3A and 3B should have the same background. This claim for duplication strengthens the validity of our data. , 
 We, the authors, sought to identify a new population of alveolar macrophages in human subjects. In panel A (top), we obtained BAL fluid and sorted cells based on SSC and FSC (granularity and size). We then used CD163 to mark the cells u2013 these are labelled as H1 (Panel A, bottom). The cells in H1 are the cells of interest. We then re-analyzed these CD163+ cells (H1) using SSC and FSC, and then for CD11b and CD14. The SSC and FSC should be quite similar in select areas of panel A (top) and panel B (top), as panel B represents a subset of Panel A. This explains why duplication would be similar in only select specific areas. Next, we took the cells in Panel A (bottom) which are CD163+ (H1) cells and these exact cells were then further analyzed in Panel B (bottom) for CD11b and CD14; these are blots are NOT identical and would not be expected to be similar. Hence the duplication strengthens the validity of the data ,