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Increased Inflammation, Hyaluronan & Respiratory Distress in Mice Overexpressing the Hyaluronan Receptor RHAMM in Macrophages
Author(s) -
Savani Rashmin C.,
Zhao Hengjiang,
Cui Zheng,
Goulet Emily,
Liao Jie,
DeLisser Horace M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a184-b
Subject(s) - bleomycin , inflammation , cd44 , receptor , macrophage , scavenger receptor , chemistry , immunology , microbiology and biotechnology , endocrinology , biology , medicine , in vitro , biochemistry , lipoprotein , chemotherapy , cholesterol
Hyaluronan (HA) and its receptors CD44 and RHAMM regulate inflammatory processes. HA‐binding peptides and RHAMM antibody inhibit macrophage accumulation after bleomycin injury. We examined bleomycin injury in mice with selective overexpression of RHAMM in macrophages generated by using the Scavenger Receptor A promoter driving a Myc‐tagged full length RHAMM cDNA. TG bone marrow‐derived macrophages (BMDM) showed increased cell surface Myc, but equal CD44 expression compared to non‐TG cells. TG macrophages had a 2‐fold increase in chemotaxis to HA and proliferation in vitro. Baseline lung expression of RHAMM and CD44 was the same in TG and non‐TG mice. However, 21 days IT bleomycin, TG mice had increased Myc‐tagged macrophages and more destruction of lung architecture as compared to non‐TG mice. Lavage HA content was higher in TG mice (Non‐TG mice: Saline: 434±60; Bleo: 2424±1032; TG mice: Saline: 354±8; Bleo: 12,283±9076, p<0.01, n=5–9/group). Non‐TG mice had increased respiratory rate (RR) from day 7 to 21. However, TG mice had higher RR as early as 4 days and continued to increase respiratory rates up to day 21 after IT bleomycin. We conclude that RHAMM promotes macrophage chemotaxis and proliferation in vitro, contributes to the accumulation of macrophages in the lung and promotes increased respiratory distress after bleomycin injury. Strategies to target RHAMM may be useful therapeutic tools to limit inflammation after lung injury.