Role of mast cells and myofibroblasts in human peritoneal adhesion formation.
OBJECTIVE
To study fibroblasts and mast cells in human peritoneal adhesions and to evaluate whether their interaction plays a role in adhesion development.


BACKGROUND
Myofibroblasts play a critical role in wound repair/fibrosis. Mast cells influence the formation of peritoneal adhesions in a rat model, and they are modulators of fibroblast functions.


METHODS
Peritoneal adhesion biopsies were processed for either histology (H&E, toluidine blue) or immunohistochemistry (tryptase, laminin, collagen type IV and VIII, and alpha-SMA) or grown as explants for obtention of fibroblasts. The effects of mast cell (HMC-1) sonicate and selected mast cell mediators and cytokines on fibroblast proliferation ([ (3)H]thymidine) and collagen synthesis ([ (3)H]proline) and on fibroblast contractile activity (tridimensional collagen lattice) were evaluated. Mast cell mediators influencing fibroblast proliferation were partially characterized by enzymatic susceptibility and FPLC gel filtration column chromatography.


RESULTS
Most of the fibroblasts in peritoneal adhesions were identified as alpha-SMA-positive myofibroblasts. Mast cell hyperplasia was observed and more than one third of the mast cells were degranulated. Few mast cells showed a faint staining for laminin or collagen type IV and VIII. Mast cell sonicate increased fibroblast proliferation and contractile activity while decreasing collagen synthesis. Mast cell sonicate proliferating activities were found to be proteinase-sensitive with a molecular weight of more than 158 kd, of approximately 40 kd, and of less than 10 kd. TGF-beta and tryptase enhanced collagen synthesis; TNF-alpha and chymase decreased it. None of the selected mediators increased fibroblast proliferation.


CONCLUSIONS
Myofibroblasts are the main connective tissue cells present in human peritoneal adhesions, and mast cells play a direct role in peritoneal adhesion formation.
Xu
Xiang
X
Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Rivkind
Avraham
A
Pappo
Orit
O
Pikarsky
Alon
A
Levi-Schaffer
Francesca
F
D002455:Cell Division; D002478:Cells, Cultured; D053818:Chymases; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D010532:Peritoneal Diseases / Q000473:pathology / Q000503:physiopathology*; D012697:Serine Endopeptidases / Q000494:pharmacology; D000267:Tissue Adhesions / Q000473:pathology / Q000503:physiopathology; D053802:Tryptases
D016207:Cytokines; D006632:Histamine; D003094:Collagen; D012697:Serine Endopeptidases; D053818:Chymases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases