HDM allergens are getting delivered into the airways by intranasal administration of allergen solutions where they induce airway inflammation. For OVA, you may also use aerosol challenge, but this method is problematic for the clinically relevant HDM allergens.. But both methods induce airway inflammation in the OVA model and we are using the intranasal challenge method in our lab for both OVA and HDM models.

Hi Dung, which model are you using? It does need inhalation provocation (nasal provocation = inhalation and according to the amount instilled, there is a certain amount reaching the lower airways: ref Am J Physiol Lung Cell Mol Physiol 282: L833–L839, 2002). It's harder to get HDM in aerosol and nasal instillation is a more accurate way to determine the exact amount inhaled by one mouse. The big difference with the OVA-model however, is that you don't need the ip sensitization.

Hope this helps? Cheers, Valerie

OVA is a well-used and characterized model and there are several good reviews available see Kumar for a discussion of the model Front Physiol. 2012;3:312. doi: 10.3389/fphys.2012.00312). DiGiovanni from Mark Inman's lab also used a combined OVA and HDM exposure (see Dis Model Mech. 2009 May-Jun; 2(5-6): 275–282) and the paper has several good references for either technique. Jordana's lab, a colleague of Inman, also uses HDM extensively (see Am J Respir Crit Care Med. 2004 Feb 1;169(3):378-85; J Immunol. 2004 Nov 15;173(10):6384-92). OVA results in airway remodelling and airway hyperresponsiveness, but the protocol relies on a two step process: 1. systemic sensitization with OVA conjugated with an aluminum adjuvant, 2. Pulmonary exposure via OVA aerosolization. Multiple inhalation exposures result in the recruitment of inflammatory cells to the lung and AHR (see Kumar). HDM relies on inhalation of the allergen, which is placed in the nose of a transiently anesthetized mouse. Jordana and Inman have suggested HDM may be a better model (see Kumar as well as Jordana & Inman for discussion). There are also a range of tools to assess AHR, which is a critical outcome measure for either model ( see Front Physiol. 2012;3:491. doi: 10.3389/fphys.2012.00491). Cheers, John

Hi you all, thank you very much for your clear explanations, very helpful answers as well as the interesting refs. :-)

First, let me declare a potential conflict: our company Indoor Biotechnologies manufactures purified natural and recombinant allergens. However, since my days in academia (University of Virginia), we have long held the view that there are flaws in both OVA and HDM models of asthma. OVA is a relatively minor food allergen and has been used mainly because it is inexpensive and readily available. Use of OVA is fundamentally no different from using other model protein antigens, such as lysozyme. HDM models are a step up, but the problem here is that the HDM used by different groups is not standardized, and even if standardized HDM is used, there is often little evidence that the inflammatory responses generated are actually caused by mite allergens, rather than other antigens and biologics in HDM extract. If one follows the logic of using HDM, then egg extract should be used instead of OVA!

So my advice to Duc is to think carefully about the consequences of using either of these antigens. Models using HDM, need to evaluate antibody and cellular responses to the major allergens, e.g. Der p 1, Der p 2 and others, as well as consider the potential role of endotoxin, chitin and other potential adjuvants in HDM extracts, if they are to pinpoint the mechanisms of allergic inflammation and AHR.

Dear Dr. Chapman,

Thank you very much for your advices. You are right, HDM extract contains not only mite proteins but also other allergens like you said, that's why by HDM model besides Eosinophils the numbers of Neutrophil, Macrophages are also increased, whereas OVA-Model characterized by increased Eosinophils. It is said, that HDM model mimics very well for human svere asthma (characterize by neutrophilic inflammation).

Actually I do not know how many kinds of HMD extracts available for mouse models and which is good for asthma mouse model. Are there any works showed the differentiation of Der p 1, Der p 2 or others on the allergic inflammation of the mouse?