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Toxicology assessment using human lung tissue models is critical and complementary for determining the hazards for aerosolized materials. In the present study, we investigated the functional, morphological and reactivity features of reconstituted human airway epithelium (MucilAir™) derived with cells from healthy and asthmatic donors. Tissues were combined with primary human monocyte derived macrophages (MDMs), and response to single Dörentrup Quartz (DQ12) dosage (10 μg/cm2) exposure over 10 days was investigated. Our study showed that DQ12 in healthy and asthmatic tissues with or without MDMs did not affect cell viability and tight junctions’ formations for up to 10 days. Pre-stained macrophages seeded on top of the healthy tissues moved towards the insert's edges, whereas a more constrained movement was observed for macrophages seeded on top of the asthmatic tissues. The reduced macrophage motility in asthmatic tissues can be attributed to stronger mucus production under pathophysiological, i.e., asthmatic, conditions and related restriction of the cilia beating effect. In addition, we found that in healthy tissues, the overexpression of transforming growth factor (TGF)-β and interleukin (IL)-8 was more pronounced following exposure to DQ12, but the addition of MDMs mitigated the inflammatory reaction of DQ12. Our findings emphasize the potential key role of macrophages added to the 3D human airway epithelia model in orchestrating the significant inflammatory responses generated by DQ12 exposure.