Lymphocyte-independent connective tissue mast cells populate murine synovium.
OBJECTIVE
Mast cells (MCs) are a heterogeneous population of tissue-resident bone marrow-derived cells; distinct MC subpopulations are situated at specific microanatomic locations. The phenotype of the murine synovial MC remains undefined. Since MCs have been implicated in the pathogenesis of inflammatory arthritis, we sought to define the phenotype of the murine synovial MC population in normal and arthritic joints. We also examined the contribution of lymphocytes to synovial MC physiology.


METHODS
The MC phenotype in healthy and K/BxN serum transfer-induced arthritic synovial tissue was defined using immunohistochemical staining of prototypic MC-specific proteases (murine MC proteases [mMCP] 1, 2, 4, 5, 6, and 7) (chymases and tryptases). MC numbers and density were determined by histomorphometry in healthy and arthritic synovia. The lymphocyte contribution to MC populations was assessed using RAG-null mice.


RESULTS
We found that synovial MCs display a connective tissue mast cell (CTMC) phenotype in both normal and arthritic synovial tissue, which expresses mMCP-4, -5, -6, and -7, but not mMCP-1 or mMCP-2. In addition, MC hyperplasia was seen in the arthritic synovium. In RAG-null mice, the phenotype and degree of MC hyperplasia were identical to those observed in normal mice with and without arthritis. Furthermore, in contrast to skin CTMCs, all synovial MCs expressed mMCP-6, demonstrating discrete differences between synovial CTMCs and other anatomic CTMC populations.


CONCLUSIONS
Our findings demonstrate that the murine synovial MC population is composed of lymphocyte-independent CTMCs and identify arthritic synovium as a model system by which to gain insight into the poorly understood physiology of CTMCs in chronic inflammation.
Shin
Kichul
K
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Gurish
Michael F
MF
Friend
Daniel S
DS
Pemberton
Alan D
AD
Thornton
Elisabeth M
EM
Miller
Hugh R
HR
Lee
David M
DM
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000503:physiopathology*; D018932:Chemokine CCL2 / Q000032:analysis; D003238:Connective Tissue / Q000502:physiology*; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000502:physiology*; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D018945:Monocyte Chemoattractant Proteins / Q000032:analysis*; D013583:Synovial Membrane / Q000166:cytology / Q000502:physiology* / Q000503:physiopathology
C103558:Ccl12 protein, rat; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018945:Monocyte Chemoattractant Proteins