Flow cytometric analysis of mononuclear phagocytes in nondiseased human lung and lung-draining lymph nodes

A. Nicole Desch, Sophie L. Gibbings, Rajni Goyal, Raivo Kolde, Joe Bednarek, Tullia Bruno, Jill E. Slansky, Jordan Jacobelli, Robert Mason, Yoko Ito, Elise Messier, Gwendalyn J. Randolph, Miglena Prabagar, Shaikh M. Atif, Elodie Segura, Ramnik J. Xavier, Donna L. Bratton, William J. Janssen, Peter M. Henson, Claudia V. Jakubzick

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Rationale: The pulmonary mononuclear phagocyte system is a critical host defense mechanism composed of macrophages, monocytes, monocyte-derived cells, and dendritic cells. However, our current characterization of these cells is limited because it is derived largely from animal studies and analysis of human mononuclear phagocytes from blood and small tissue resections around tumors. Objectives: Phenotypic and morphologic characterization of mononuclear phagocytes that potentially access inhaled antigens in human lungs. Methods: We acquired and analyzed pulmonary mononuclear phagocytes from fully intact nondiseased human lungs (including the major blood vessels and draining lymph nodes) obtained en bloc from 72 individual donors. Differential labeling of hematopoietic cells via intrabronchial and intravenous administration of antibodies within the same lobe was used to identify extravascular tissue-resident mononuclear phagocytes and exclude cells within the vascular lumen. Multiparameter flow cytometry was used to identify mononuclear phagocyte populations among cells labeled by each route of antibody delivery. Measurements and Main Results: We performed a phenotypic analysis of pulmonary mononuclear phagocytes isolated from whole nondiseased human lungs and lung-draining lymph nodes. Five pulmonary mononuclear phagocytes were observed, including macrophages, monocyte-derived cells, and dendritic cells that were phenotypically distinct from cell populations found in blood. Conclusions: Different mononuclear phagocytes, particularly dendritic cells, were labeled by intravascular and intrabronchial antibody delivery, countering the notion that tissue and blood mononuclear phagocytes are equivalent systems. Phenotypic descriptions of the mononuclear phagocytes in nondiseased lungs provide a precedent for comparative studies in diseased lungs and potential targets for therapeutics.

Original languageEnglish
Pages (from-to)614-626
Number of pages13
JournalAmerican journal of respiratory and critical care medicine
Volume193
Issue number6
DOIs
StatePublished - Mar 15 2016

Keywords

  • Dendritic cells
  • Macrophages
  • Monocytes
  • Mononuclear phagocytes
  • Pulmonary

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