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Increased Inflammatory Responses In Mice Overexpressing The Hyaluronan Receptor RHAMM In Macrophages
Author(s) -
Cui Zheng,
Zhao Hengjiang,
Cao Gaoyuan,
DeLisser Horace M,
Savani Rashmin C
Publication year - 2006
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.20.5.a1337-e
Hyaluronan (HA) and its receptors CD44 and RHAMM have been implicated in regulating the inflammatory process. HA‐binding peptides and antibody to RHAMM inhibit lung macrophage accumulation after bleomycin injury. We therefore overexpressed RHAMM in macrophages in vitro as well as in transgenic mice. Stable transfection of a FLAG‐tagged full‐length mouse RHAMM cDNA in murine RAW264.7 macrophages was confirmed by RT‐PCR, western blots and immunofluorescence. Parent and LacZ‐transfected cells were used as controls. RHAMM overexpressing cells had an approximately 2.5‐fold increase in both chemotactic response to HA and proliferation as compared to controls. A transgenic construct using the macrophage‐specific Scavenger Receptor A promoter to drive a myc‐tagged full length RHAMM cDNA was used to generate transgenic (TG) lines. TG bone marrow‐derived macrophages (BMDM) showed a 2‐fold increase in both chemotaxis to HA and proliferation as compared to non‐TG controls. Further, TG mice given IP thioglycollate showed equal peritoneal recruitment of neutrophils at day 1, but significantly higher macrophage accumulation by day 3 as compared to WT controls. Intratracheal bleomycin in TG mice resulted in increased macrophage accumulation and more destruction of lung architecture as compared to WT mice. We conclude that RHAMM promotes macrophage chemotaxis and proliferation, and contributes to the accumulation of macrophages in areas of inflammation. Strategies to target RHAMM may be useful therapeutic tools to limit inflammation after injury.