Targeting Mac-1-mediated leukocyte–RBC interactions uncouples the benefits for acute vaso-occlusion and chronic organ damage

Grace Chen, Jungshan Chang, Dachuan Zhang, Sandra Pinho, Jung Eun Jang, Paul S. Frenette

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Vaso-occlusive crisis (VOC) is one of the most common complications of sickle cell disease (SCD). Recurrent episodes of VOC may cause irreversible organ damage and early mortality in patients with SCD. Emerging evidence suggests that VOC arises from a complex cascade that involves interactions among multiple blood and endothelial cells in the vasculature. Previous studies have identified αMβ2 integrin (Mac-1) as a critical molecule that mediates heterotypic interactions between red blood cells (RBCs) and adherent leukocytes and promotes VOC in SCD mice. Here, we show that RBC–leukocyte interactions are significantly diminished in Mac-1-deficient SCD mice, leading to an improvement of blood flow rates and prolonged survival time in a tumor necrosis factor-alpha and surgical-trauma-induced VOC model. Mac-1-deletion, however, was not sufficient to reduce SCD-related chronic organ damage. Our results thus suggest uncoupled mechanisms between acute VOC benefits and the long-term complications of SCD that should be considered in future clinical trials.

Original languageEnglish (US)
Pages (from-to)940-946
Number of pages7
JournalExperimental Hematology
Volume44
Issue number10
DOIs
StatePublished - Oct 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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