Allergy-related biologic actions and effects evoked by HDM protease allergens
| Sphere of Action | Action or Effect | Allergen or Extract | References |
|---|---|---|---|
| Mucosal defense | Cleavage of tight junctions/reduced epithelial barrier function/allergen delivery | HDM fecal pellet extract, Der p 1, Der f 1, Der p 3, Der p 6 | Herbert et al. (1990, 1995), Winton et al. (1998), Wan et al. (1999, 2000, 2001), Nakamura et al. (2006); ADI program—data on file |
| Disruption of epithelial adherens junctions | Der p 1 (directly and indirectly via ADAM 10) | Wan et al. (1999); ADI program—data on file | |
| Inactivation of airway antiproteases | Der p 1 | Kalsheker et al. (1996), Brown et al. (2003) | |
| Epithelial-mesenchymal transition | HDM extract | Heijink et al. (2010a), Frisella et al. (2011) | |
| Inactivation of surfactant proteins | Der p 1, Der f 1 | Deb et al. (2007) | |
| IgE-independent mast cell stimulation | Der p 1, HDM extract | Machado et al. (1996) | |
| Activation of NLRP3 inflammasome and apoptosis | HDM extract, Der p 1 | Winton et al. (1998), Baker et al. (2003), Frisella et al. (2011) | |
| Cell signaling | Prothrombinase activity | HDM fecal pellet extract, Der p 1 | Zhang et al. (2016, 2018) |
| PAR-1 and PAR-4 activation | Der p 1 (indirectly as prothrombinase) | Zhang et al. (2016); ADI program—data on file | |
| PAR-2 activation | HDM fecal pellet extract, Der p 1, Der p 3, Der p 9 | Sun et al. (2001), Asokananthan et al. (2002), Jeong et al. (2008), Kato et al. (2009), Cho et al. (2012), de Boer et al. (2014), Post et al. (2014), Zhang et al. (2016), Reddy and Lerner (2017) | |
| PAR-1 inactivation | Der p 1 | Asokananthan et al. (2002) | |
| PAR-2 inactivation | Der p 1 | Adam et al. (2006), Kato et al. (2009) | |
| PAR-1 and PAR-2 upregulated expression | Der p 1 | Shi et al. (2010) | |
| Mas-related G-protein–coupled receptor activation | Der p 1 | Reddy and Lerner (2017) | |
| EGFR activation in epithelial cells | Der p 1 (indirectly as prothrombinase) | Zhang et al. (2016, 2018); ADI program—data on file | |
| Pannexon gating in epithelial cells | Der p 1 (indirectly as prothrombinase) | Zhang et al. (2016, 2018); ADI program—data on file | |
| ATP release from epithelial cells | Der p 1 (indirectly as prothrombinase) | Zhang et al. (2016, 2018); ADI program—data on file | |
| ADAM 17 activation in epithelial cells | Der p 1 (indirectly as prothrombinase) | Chen et al. (2017), Zhang et al. (2018) | |
| ADAM 10 activation in epithelial cells | Der p 1 (indirectly as prothrombinase) | Chen et al. (2017); ADI program—data on file | |
| ADAM 8 activation in epithelial cells | Der p 1 (indirectly as prothrombinase) | ADI program—data on file | |
| Cleavage of low-affinity IgE receptor (CD23) | Der p 1 (directly and indirectly via ADAM 10) | Schulz et al. (1995); ADI program—data on file | |
| Activation of endogenous interstitial prothrombinase | HDM extract (due to Der p 1) | Zhang et al. (2016); ADI program—data on file | |
| Regulation of gene expression and exploitation of antioxidant deficits | ROS generation | Intracellular ROS by HDM fecal pellet extract, Der p 1 in epithelial cells, Der f 1 in neutrophils | Fukunaga et al. (2011), Zhang et al. (2016, 2018), Chen et al. (2017) |
| Immune activation and allergic polarization | Breaking of immune tolerance | HDM extract, Der p 1 | Gough et al. (1999, 2001, 2003); ADI program—data on file |
| Suppression of indoleamine 2,3-dioxygenase | Der p 1 | Maneechotesuwan et al. (2009) | |
| TLR4 ligation | HDM extract, Der p 1 (indirectly as prothrombinase) | Zhang et al. (2018); ADI program—data on file | |
| Bioactivating cleavage of IL-33 | Der p 1 | Cayrol et al. (2018) | |
| Cytokine/chemokine expression and release (e.g., IL-33, TSLP, CCL2, CCL20, GM-CSF, IL-8, IL-13, etc.) | HDM extract, Der p 1, Der p 3, Der p 6, Der p 9 | King et al. (1998), Pichavant et al. (2005), Adam et al. (2006), Kauffman et al. (2006), Ogawa et al. (2008), Kato et al. (2009), Shi et al. (2010), Arlian and Morgan (2011); ADI program—data on file | |
| Cleavage of IL-2R (CD25) | Der p 1 | Schulz et al. (1998) | |
| Antigen-presenting cell recruitment and activation | Dendritic antigen-presenting cell recruitment | HDM extract, Der p 1 | Pichavant et al. (2005), Robinson et al. (2012); ADI Program—data on file |
| Cleavage of DC-SIGN/DC-SIGNR | Der p 1 | Furmonaviciene et al. (2007) | |
| Interaction with viral RNA sensors | Transductional convergence with signaling from TLR3 and TLR7 | HDM fecal pellet extract, Der p 1 | Zhang et al. (2018); ADI Program—data on file |
| Effector mechanisms | Leukocyte recruitment | Der p 1, HDM extract | Robinson et al. (2012), Newton et al. (2014); ADI program—data on file |
| Kinin generation from low- and high-molecular-weight kininogens | Der f 3 | Takahashi et al. (1990), Maruo et al. (1991), Maruo et al. (1993) | |
| Decreased cysteine protease inhibitory activity of kininogens | Der f 3 | Maruo et al. (1993) | |
| Anaphylatoxin generation | Der f 3 | Maruo et al. (1997) | |
| IgE-independent “pseudoallergic” bronchoconstriction | Der p 1, HDM extract | ADI program—data on file |
DC-SIGNR, DC-SIGN receptor; EGFR, epidermal growth factor receptor; GM-CSF, granulocyte macrophage-colony stimulating factor.