IgA sensitizes airway smooth muscle to histamine

Abstract

Rationale IgA is an important defense against infectious pathogens, which are common triggers of asthma symptoms. We recently reported that primary cell cultures of human airway smooth muscle (ASM) cells express the IgA receptor (pIgR) that binds polymeric IgA (pIgA) but not monomeric IgA (mIgA), and that pIgA increases cytosolic calcium - a necessary prequel to smooth muscle contraction and therefore bronchoconstriction. In this study, we asked if pIgA sensitizes ASM to histamine-induced responses. Methods Cytosolic calcium was measured in Fura2-loaded human ASM cells stimulated first with histamine 10 −6M and then treated for 2h with buffer, pIgA or mIgA. Post-incubation histamine-induced cytosolic calcium concentrations were compared to the pre-incubation response. Tension was measured in isolated canine tracheal ASM strips first in response to histamine 10 −5M and then treated for 4h with buffer, pIgA or mIgA. Post-incubation histamine-induced tension was compared to the pre-incubation response. Results Incubation with pIgA (0.12 μg/ml) significantly augmented the histamine-induced increase in cytosolic calcium in human ASM cells compared to mIgA (12 μg/ml) or buffer (p<0.05). Similarly, incubation with pIgA (6 μg/ml) appreciably enhanced histamine-induced increases in tension (by 2g) in canine tracheal ASM strips compared to mIgA 3 μg/ml (0.36g) or buffer (0.35g; p<0.05). Conclusions Incubation with pIgA sensitizes human ASM cells and canine tracheal ASM strips to histamine. Because IgA is an important epithelial defense against viral and bacterial attachment, functional responses to IgA in ASM may account, at least in part, for the worsening of symptoms during upper respiratory tract infections in patients with allergic asthma.