Expression and regulation of antimicrobial peptides in articular joints.
Articular joint infection is a surprisingly rare event considering the frequency of joint arthrocentesis and other invasive procedures applied to limb joints. This observation led us to the hypothesis that a local "chemical shield" in the form of antimicrobial proteins provides synovial membrane and articular cartilage with resistance to infection. We subsequently began a systematic analysis of in vitro and in vivo antimicrobially active proteins in healthy articular joints and in disease states such as pyogenic arthritis, rheumatoid arthritis, and osteoarthritis. An anatomical approach with systematic characterization combined with antimicrobial testing revealed expression and production of human antibiotic peptides and proteins. In this review, we focus on the most prominent antimicrobial proteins in articular joints, which we have identified as lysozyme, lactoferrin, secretory phospholipase A2, RNase 7, CAP37, the cathelicidin LL37, and especially the human beta-defensin-2 and -3 (HBD-2/-3). Activation pathways and possible antimicrobial functions are discussed and the involvement in non-antimicrobial processes such as tissue remodelling is also considered.
Varoga
Deike
D
Department of Orthopaedic Surgery, University Hospital of Schleswig-Holstein, Campus Kiel, Michaelisstrasse 1, 24105 Kiel, Germany. d.varoga@orthop.uni-kiel.de
Pufe
Thomas
T
Mentlein
Rolf
R
Kohrs
Susanne
S
Grohmann
Susanne
S
Tillmann
Bernhard
B
Hassenpflug
Joachim
J
Paulsen
Friedrich
F
D002358:Cartilage, Articular / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007592:Joint Diseases / Q000503:physiopathology; D013583:Synovial Membrane / Q000502:physiology; D023083:beta-Defensins / Q000235:genetics*
D023083:beta-Defensins