Expression of CD44 variants in human inflammatory synovitis

Journal Article · Wed Nov 01 04:00:00 EST 1995 · Journal of Clinical Immunology

DOI:https://doi.org/10.1007/BF01541320· OSTI ID:182168

Hale, L P ^[1]; Haynes, B F; McCachren, S ^[2]

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1. Duke Univ. Medical Center, Durham, NC (United States)
2. Duke Univ. Arthritis Center, Durham, NC (United States)

The cell surface hyaluronate receptor CD44 has previously been shown to have immunomodulatory activity and to be upregulated in inflammatory synovitis. Since these findings were reported, the genomic structure of CD44 has been delineated, and multiple splice variants have been described. Therefore, we determined which CD44 variant exons are present during inflammatory synovitis by a combination of Northern blot analysis and reverse transcription followed by polymerase chain reaction amplification of synovial RNA. Immunohistochemical staining was used to define the sites of expression of individual v6 and v9 exons in synovial tissue. The standard (S) or hematopoietic isoform, CD44S, was the predominant form of CD44 expressed in synovium and was expressed by most cell types. Other isoforms, containing alternatively spliced exons in the proximal extracellular domain, were found by RT-PCR, but at lower levels than CD44S. The second most prevalent form was CD44E, which has an insertion of three exons (v8-v10) in the proximal extracellular domain. Immunohistochemical studies showed that reactivity with v9-specific antibodies was primarily in macrophages, particularly those in the synovial lining layer. CD44 exon v6, previously reported to be important in immune activation and in epithelial tumor metastasis, was also expressed in synovial lining cells and in occasional synovial interstitial cells. The presence of CD44 variants containing v9 in rheumatoid synovial macrophages may be important in the adhesion and activation of mononuclear phagocytes in the synovium and, thus, may be a target for novel antiinflammatory therapies in the future. The role of CD44 isoforms in cellular adhesion, immune activation, and joint erosion in inflammatory synovitis deserves further study. 7 figs., 2 tabs., 56 refs.

• Sponsoring Organization: USDOE
• OSTI ID: 182168
• Journal Information: Journal of Clinical Immunology, Journal Name: Journal of Clinical Immunology Journal Issue: 6 Vol. 15; ISSN JCIMDO; ISSN 0271-9142
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ANIMAL CELLS
ANTIBODIES
BONE JOINTS
DNA HYBRIDIZATION
ENZYMES
EXONS
GENE REGULATION
GENES
IMMUNE SYSTEM DISEASES
INFLAMMATION
MUTATIONS
OLIGONUCLEOTIDES
POLYMERASE CHAIN REACTION
PROBES
PROTEINS
RECEPTORS
RHEUMATIC DISEASES
SPLICING
TRANSCRIPTION