THE HUMAN CARDIAC MAST-CELL - LOCALIZATION, ISOLATION, PHENOTYPE, ANDFUNCTIONAL-CHARACTERIZATION

We have isolated and characterized the human cardiac mast cell (CMC) a nd compared this novel mast cell (MC, type with MC obtained from uteru s, skin, and lung. Heart tissue was obtained from 14 patients with car diomyopathy (CMP, heart transplantation). CMC were isolated by enzymat ic digestion using collagenase, pronase-E. hyaluronidase, and DNAse. S ubstantial amounts of CMC (0.5% to 1.5% of isolated cells) were found in the atrial appendages but not in ventricular digests or other sites of the heart (<0.1%). In situ staining of atrial tissue revealed the presence of CMC in the myocardium (2.16 +/- 0.7 MC/mm(2)), endocardium (2.24 +/- 0.9 MC/mm(2)), and epicardium. As assessed by combined tolu idine blue/immunofluorescence staining with monoclonal antibodies (MoA bs), isolated CMC expressed surface IgE, the receptor for stem cell fa ctor (c-kit receptor/CD117), the p24 antigen (CD9), the Pgp-1 homing r eceptor (CD44), the pan leukocyte antigen (CD45), and the ICAM-1 antig en (CD54). CMC were not recognized by MoAbs to lymphocyte function ass ociated antigen 2 (LFA-2; CD2), T-cell receptor (TcR; CD3), T4 antigen (CD4), LFA-1 alpha-chain (CD11a), C3biR alpha-chain (CD11b), CR4 alph a-chain (DC11c), LPS-R related Ag (CD14), 3FAL/x-hapt en (CD15), Fc ga mma RIII (CD16), lactosylceramid (CDw17), the B-cell antigen CD19, or CR1 (CD35). In situ expression of leukocyte antigens on CMC was demons trable by indirect immunoperoxidase staining technique and double-labe ling immunohistochemistry. Almost all CMC (90%) reacted with MoAbs aga inst tryptase chymase thus were MC(TC). Cardiac mast cells were also s tained by the heparin-binding dye Berberine sulfate and expressed meas urable amounts of histamine (4.6 +/- 1.4 pg per cell). Cross linking o f either IgE receptor or SCF receptor (c-kit) on CMC resulted in hista mine secretion (non-specific release: <6% of total histamine, alpha lg E induced: 12% to 52%; SCF-induced release: 9% to 18%), whereas neithe r substance P (a skin MC agonist) nor the basophil agonist FMLP showed an effect on CMC. Together, the CMC is an MC(TC) primarily located in the appendage of the atrium. This novel type of MC exhibits surface m embrane antigen and functional properties similar to those of lung and uterus MC. (C) 1994 by The American Society of Hematology.