Differential effects of chemoattractants on mast cell recruitment in vivo.

Rats were injected with rat recombinant (rr) IL3, rrSCF, rrIL-3+rrSCF, rrRANTES and LTB4. Six hours after subcutaneous injection of rrIL-3 or rrIL-3+rrSCF, there was an increase in mast cell numbers in the skin and spleen. Peritoneal mast cells were recruited following i.p. injection of rrIL-3, but with rrIL-3+rrSCF recruitment was delayed. Immunostaining with a mast cell specific antibody showed that immature orthochromatic mast cells were being recruited. rrIL-3 induced recruitment of mast cells to the peritoneal cavity was blocked by anti-integrin antibodies. Mast cell recruitment depended on the target tissue and the time of exposure to the chemoattractant.

Rat embryonic mast cells originate in the AGM.

Mast cells originate from pluripotent hematopoietic stem cells. Two mast cell specific antibodies, mAbsAA4 and BGD6, have previously been used to identify and study committed mast cell precursors (MCcps) in the bone marrow of adult mice and rats. However, the embryonic origin of MCcps is still not known. In the present study, we identified MCcps in rat embryos using these previously characterized mast cell specific antibodies. The MCcps were found in the AGM (aorta-gonad-mesonephros) region of rat embryos at E11.5. These cells were BGD6+, CD34(+), c-kit(+), CD13(+), FcεRI(-), AA4(-) CD40(-), and Thy-1(-). By PCR the cells contained message for the α and ß subunits of FcεRI and mast cell specific proteases. In vitro, the MCcps differentiated into metachromatic mast cells. With age of gestation the percent of MCcps diminished while the percent of mast cell progenitors increased. An increased knowledge of the biology and embryonic origin of mast cells may contribute to a greater understanding of allergy, asthma, and other mast cell related diseases.

Expression of mast cell proteases correlates with mast cell maturation and angiogenesis during tumor progression.

Tumor cells are surrounded by infiltrating inflammatory cells, such as lymphocytes, neutrophils, macrophages, and mast cells. A body of evidence indicates that mast cells are associated with various types of tumors. Although role of mast cells can be directly related to their granule content, their function in angiogenesis and tumor progression remains obscure. This study aims to understand the role of mast cells in these processes. Tumors were chemically induced in BALB/c mice and tumor progression was divided into Phases I, II and III. Phase I tumors exhibited a large number of mast cells, which increased in phase II and remained unchanged in phase III. The expression of mouse mast cell protease (mMCP)-4, mMCP-5, mMCP-6, mMCP-7, and carboxypeptidase A were analyzed at the 3 stages. Our results show that with the exception of mMCP-4 expression of these mast cell chymase (mMCP-5), tryptases (mMCP-6 and 7), and carboxypeptidase A (mMC-CPA) increased during tumor progression. Chymase and tryptase activity increased at all stages of tumor progression whereas the number of mast cells remained constant from phase II to III. The number of new blood vessels increased significantly in phase I, while in phases II and III an enlargement of existing blood vessels occurred. In vitro, mMCP-6 and 7 are able to induce vessel formation. The present study suggests that mast cells are involved in induction of angiogenesis in the early stages of tumor development and in modulating blood vessel growth in the later stages of tumor progression.