Fig. 7.
Rescuing calcium voltage-gated channel subunit alpha1 C (CaV1.2) expression exacerbates antigen induced pulmonary inflammation (AIPI) in conditional knockout (CKO) mice. (A) CKO Mice received wild type (WT) bone marrow mast cells (BMMCs) transplantation and AIPI induction. (B) Hematoxylin and eosin (H&E), Masson, and periodic acid-Schiff (PAS) stainings of lung sections of CKO mice with or without WT BMMC transplantation in AIPI (left) or phosphate-buffered saline (PBS) (right) treatments. (C) Airway hyperreaction (AHR) of CKO mice with or without WT BMMC transplantation in AIPI (left) or PBS (right) treatments. (D) The numbers of eosinophils, neutrophils, and total cells as well as T helper 2 (Th2) cytokines release in bronchoalveolar lavage fluid (BALF) of CKO mice with or without WT BMMC transplantation in AIPI (left) or PBS (right) treatments. (E) CaV1.2 is involved in mast cell (MC) activation induced via Mas-related G protein-coupled receptor X2 (MrgX2). MrgX2 activation induced Ca2+ release from endoplasmic reticulum. Next, the intracellular Ca2+ activated calcium/calmodulin-dependent kinase II (CaMKII), which then phosphorylated protein kinase C (PKC). PKC phosphorylation interacted directly with CaV1.2 and caused Ser1928 phosphorylation, leading the opening of CaV1.2. Massive Ca2+ influx gave rise to MC activation. The CaV1.2 antagonists, including nimodipine (Nim), inhibited MC activation by inhibiting Ca2+ influx through CaV1.2. Experiments were repeated three times. Data are presented as the mean ± standard error of mean (SEM) and were analyzed using one-way analysis of variance (ANOVA) test. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. OVA: ovalbumin; Ach: acetylcholine; Rn: Newtonian resistance; Rrs: respiratory resistance; G: resistance of the peripheral lung; Cst: static compliance; IL: interleukin.