ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 314

Transcriptome and Surface Phenotype Analyses Suggest an Alternatively Activated (M2) Function for Hemophagocytes

Scott W. Canna1, Ana Patrícia Costa Reis2, William E. Bernal3, Kathleen E. Sullivan4, Michele E. Paessler5 and Edward M. Behrens6, 1Pediatric Rheumatology, Childrens Hospital of Philadelphia, Philadelphia, PA, 2Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, 3Division of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, PA, 4Immunology ARC 1216, The Children's Hospital of Philadelphia, Philadelphia, PA, 5Hematopathology, Childrens Hospital of Philadelphia, Philadelphia, PA, 6Rheumatology, Children's Hospital of Philadelphia, Philadelphia, PA

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: cytokines, Inflammation, macrophage activation syndrome and macrophages

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Title: Pediatric Rheumatology - Pathogenesis and Genetics

Session Type: Abstract Submissions (ACR)

Background/Purpose: Hemophagocytes (HPCs) are activated macrophages identified in situ by having engulfed other hematopoietic cells. HPCs are rarely seen in normal bone marrow, but are abundant in a variety of cytokine storm syndromes. HPCs are the pathologic hallmarks of two related diseases: Macrophage Activation Syndrome (MAS) and Hemophagocytic Lymphohistiocytosis (HLH). The function of the HPC is controversial. Some evidence suggests HPCs are inflammatory and pathogenic, while other evidence supports a housekeeping or anti-inflammatory role for these cells by pointing out their absence in some patients with overt MAS or HLH and their high expression of scavenger receptors like CD163. However, no study has yet attempted to directly phenotype these cells. Using two distinct approaches, we now show that HPCs display an M2, or anti-inflammatory phenotype.

Methods: Splenic HPCs induced in an animal model of MAS utilizing repeated Toll-like Receptor 9 (TLR9) stimulation in the context of IL-10 receptor blockade were isolated by single cell laser capture microdissection with the assistance of a board certified hematopathologist (MP). Gene expression levels of these cells were measured using microarray and compared to those of laser-captured resting splenic macrophages. Highly differentially expressed genes were verified using quantitative RT-PCR. Differential regulation of pre-determined gene sets was analyzed using a Gene Set Enrichment Analysis (GSEA). Additionally, bone marrow biopsies from patients with MAS or HLH noted to have excessive hemophagocytosis as part of their clinical evaluation were subjected to immunohistochemistry for markers of classical (M1) or alternative (M2) activation and scored by a blinded hematopathologist (MP).

Results: Of 6 treatment and 6 control samples, the RNA of 4 samples in each group were of sufficient quality for analysis. The gene sets meeting statistical significance for upregulation in HPCs were those related to the proteasome, M2 gene regulation, cytoskeleton regulation, and Nod-like receptor signaling. The gene set for M1 gene regulation was not found to be different between HPCs and resting macrophages. Human bone marrow biopsies stained for the mannose receptor and M2 marker CD206 showed HPCs with a membrane-bound staining pattern. HPCs with such staining for the M1 differentiation marker CD64 were very rarely identified.

Conclusion: For the first time, we have described the functional program of in situ HPCs as alternatively activated (M2) and potentially anti-inflammatory. This raises questions about elimination of HPCs as a therapeutic rationale, and supports future investigations into optimal treatment strategies for hemophagocytic diseases.


Disclosure:

S. W. Canna,
None;

A. P. Costa Reis,
None;

W. E. Bernal,
None;

K. E. Sullivan,
None;

M. E. Paessler,
None;

E. M. Behrens,
None.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/transcriptome-and-surface-phenotype-analyses-suggest-an-alternatively-activated-m2-function-for-hemophagocytes/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology