Do Mucosal Mast Cells Contribute to the Immediate Asthma Response?

Abstract

ABSTRACT-In rat trachea, two types of mast cells have been identified, connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs). We previously reported that CTMCs play an important role in tracheal contraction in vitro via 5-hydroxytryptamine (5-HT) release in a rat model. In this study, we investigated whether MMCs also play a role in tracheal contraction by employing mast cell-deficient (Ws/ Ws) rats and their congenic (+ /+) rats. Rats were actively sensitized with ovalbumin and challenged with it 2 weeks later. To exclude the influence of CTMCs, rats were pretreated for 7 days with compound 48 / 80 injected i.p. in increasing doses. Histological study confirmed that degranulation occurred in CTMCs, but MMCs still remained. Histamine levels in trachea decreased to 9.31% of control levels. Ovalbumin-specific IgE production showed a time-dependent increase in both Ws/ Ws and +/+ rats after sensitization with no significantly different values between the two groups. Ovalbumin challenge caused contraction of the trachea in sensitized control (+ /+) rats, but not in sensitized Ws/ Ws and compound 48 /80-pretreated +/+ rats. Ketanserin inhibited the contraction, but leukotriene antagonist ONO-1078 did not, indicating that the contraction was due to 5-HT, whereas leukotriene, a mediator specific derived from MMCs, has no significant effect. The results suggest that MMCs has minimal, if any, contribution to tracheal contraction and might have another function. Furthermore, Ws / Ws and the congenic rats provide a good model for studying the role of mast cells in the immunologic response in airways.

Two Pharmacological Phases in Antigen-Induced Immediate Airway Response in Rats

“…On the other hand, compound 48/80 did not influence EP, which was suppressed by anti-LT and anti-TXA 2 . These findings are corresponded to the effects of compound 48/80 on CTMC 5,20) and with a report on the mediator profile of CTMC. 21) Summarizing findings, QP in rat IAR appears to be mediated by the exocytosis of mediators in CTMCs, while EP in rat IAR appears to be mediated by LT and TXA 2 , which are not generated by CTMCs.…”

“…In rat airway, CTMCs and MMCs are observed in the submucosal region and epithelial layer, respectively. 19,20) Although both CTMCs and MMCs release histamine and serotonin, lipoxygenase products such as LT are predominantly generated by MMCs. 21) Ikawati et al (2000Ikawati et al ( , 2001 found in a histological study that when rats were administered compound 48/80 in increasing doses for 7 d, tracheal CTMCs were almost completely eliminated, while the number of MMCs in trachea was unaffected.…”

“…19,20) Although both CTMCs and MMCs release histamine and serotonin, lipoxygenase products such as LT are predominantly generated by MMCs. 21) Ikawati et al (2000Ikawati et al ( , 2001 found in a histological study that when rats were administered compound 48/80 in increasing doses for 7 d, tracheal CTMCs were almost completely eliminated, while the number of MMCs in trachea was unaffected. 5,20) In our experiment, pretreatment with compound 48/80 diminished but did not eliminate QP, which was suppressed by ketotifen.…”

“…21) Ikawati et al (2000Ikawati et al ( , 2001 found in a histological study that when rats were administered compound 48/80 in increasing doses for 7 d, tracheal CTMCs were almost completely eliminated, while the number of MMCs in trachea was unaffected. 5,20) In our experiment, pretreatment with compound 48/80 diminished but did not eliminate QP, which was suppressed by ketotifen. On the other hand, compound 48/80 did not influence EP, which was suppressed by anti-LT and anti-TXA 2 .…”

The contribution of mast cells to the late-phase of allergic asthma in rats

“…Mast cells are thought to cause the acute symptoms of the acute allergic inflammation by release of histamine and other lipid mediators [4]. Our previous research also discussed the role of mast cells in the EAR [5]. Mast cells are now known to contribute to recruitment and activation of secondary effector cells, in particular eosinophils, which are hallmarks of the chronic asthmatic response and airway remodeling [6].…”