Response to C3a, mast cells, and asthma

Abstract

This is in response to a “Letter to the Editor (1)” by Dr. Bradding regarding our manuscript entitled “Airway smooth muscle cells enhance C3a-induced mast cell degranulation following cell-cell contact” that was published in your journal recently (2). Dr. Bradding contends that our manuscript, which utilizes a C3a-responsive human mast cell line, is misleading because “it ignores wealth of consistent literature demonstrating that human lung mast cells and human lung fragments do not exhibit any response to C3a or C5a.” We disagree with this view for the reasons discussed below. Although studies performed in the 1980s and 1990s, showed that dispersed human lung mast cells are unresponsive to C3a and C5a (3–5), these studies did not characterize the expression of C3a receptor in mast cells and failed to consider the possibility that lung tissue may contain a subpopulation of mast cells that could be responsive to anaphylatoxins. Human mast cells (MC) consist of a mixture of at least two cell types that can be distinguished based on the protease content of their granules. It is well documented that MCTC cells (tryptaseand chymase-positive) that are found predominantly in the skin are responsive to C3a and C5a whereas MCT cells (tryptase positive) present in other tissues are unresponsive to these anaphylatoxins (6). The previous demonstration that dispersed lung mast cells did not respond to C3a or C5a probably reflects the fact that 90% of these cells are MCT cells (7). Indeed, a recent report by Oskeritzian et al. (8) showed that MCTC cells purified from a mixture of human lung mast cells are highly responsive to C5a for histamine release and leukotriene C4 generation, mediators that promote airway hyperreactivity. Most importantly, mast cells that infiltrate into the airway smooth muscle in asthma are positive for both tryptase and chymase (9). Given that MCTC cells are also responsive to C3a for mediator release (10, 11), we argue that a C3a responsive human mast cell line is an appropriate in vitro cellular model to delineate the signaling pathways involved in mast cell-airway smooth cell interaction relevant to asthma. REFERENCES