Calcium channel blockers suppress the contact hypersensitivity reaction (CHR) by inhibiting antigen transport and presentation by epidermal Langerhans cells in mice

Abstract

SUMMARYSince Langerhans cells (LC) are the principal antigen-presenting cells among epidermal cells, treatments suppressing LC function may inhibit CHR. Although calcium channel blockers (CCB) have been shown to suppress the functions of several immunologically active cells, little is known about their effect on LC. In this study we show that pretreatment with topical 1% nifedipine or verapamil HCl significantly suppressed both the sensitization and elicitation phases of a CHR in mice. We then investigated whether CCB affected LC. Flow cytometric analysis of regional lymph node cells obtained 24 h after applying FITC demonstrated that topical CCB treatment significantly reduced the percentage of FITC þ NLDC-145 þ cells, suggesting that CCB had suppressed antigen transport by LC. In vitro treatment with nifedipine or verapamil significantly suppressed the antigen-presenting capacity of LC in a dose-dependent manner. In addition, in vitro CCB treatment reduced the percentage of class II MHC antigen-positive epidermal cells and significantly suppressed class II MHC and B7-1 levels in LC, as determined by flow cytometry and reverse transcriptase-polymerase chain reaction, whereas surface expression of B7-2 and mRNA was only weakly reduced. Neither expression of CD45 nor the percentage of CD45 þ cells were affected, suggesting that the effects of CCB on LC were not due to cytotoxicity. Our results suggest that CCB inhibit CHR, at least in part, by suppressing the functions of LC.

Topical Nifedipine With Lidocaine Ointment vs. Active Control for Treatment of Chronic Anal Fissure

“…41,42 Data reported in the present study cannot justify this assumption, and further studies are required to explain the mechanism of healing of fissure. However, the subsequent formation of an inflammatory infiltrate from a chronic anal fissure is associated with continuous hypertonicity of the internal sphincter, a microcirculatory disturbance, 3 and the presence of fibrosis and myositis throughout the internal anal sphincter.…”

Differential gene expression analysis identifies murine Cacnb3 as strongly upregulated in distinct dendritic cell populations upon stimulation

“…Interestingly, while in human monocyte-derived DCs the L-type VDCC inhibitor nifedipine was reported to block both engulfment of apoptotic bodies and IL-12 production induced by lectin-crosslinking (Poggi et al, 1998), murine BM-DCs were shown to lack VDCC activity (Hsu et al, 2001). Notably, nifedipine was reported to inhibit the maturation of murine LCs (Katoh et al, 1997), which prompted us to apply this inhibitor during stimulation of SP37A3 cells. In contrast to the findings of Katoh et al (1997) for LCs, inhibition of L-type VDCCs in SP37A3 cells exerted no detrimental effects on the stimulation-associated acquisition of potent T cell stimulatory capacity.…”

“…Notably, nifedipine was reported to inhibit the maturation of murine LCs (Katoh et al, 1997), which prompted us to apply this inhibitor during stimulation of SP37A3 cells. In contrast to the findings of Katoh et al (1997) for LCs, inhibition of L-type VDCCs in SP37A3 cells exerted no detrimental effects on the stimulation-associated acquisition of potent T cell stimulatory capacity. Taken together, these results show that the various DC populations greatly differ in the functional activity of Ca 2+ channel types during DC stimulation, and accordingly in the qualitative contribution of these Ca 2+ channels to DC maturation.…”

Fundamental Ca2+ Signaling Mechanisms in Mouse Dendritic Cells: CRAC Is the Major Ca2+ Entry Pathway

“…Just how DHPs mobilize Ca 2ϩ is unclear. Nevertheless, the signaling pathway deserves further attention because nifedipine has been found to modulate numerous DC functions, including inhibition of Ag processing (42), apoptotic body engulfment, and IL-12 secretion (26).…”