The sensitivity of alveolar macrophages to substrate properties has been described in a recent paper (Féréol et al., Cell Motil. Cytoskel. 63 (2006), 321-340). It is presently re-analyzed in terms of F-actin structure (assessed from 3D-reconstructions in fixed cells) and mechanical properties (assessed by Magnetic Twisting Cytometry experiments in living cells) of cortical and deep cytoskeleton structures for rigid plastic (Young Modulus: 3 MPa) or glass (70 MPa) substrates and a soft (approximately 0.1 kPa) confluent monolayer of alveolar epithelial cells. The cortical cytoskeleton component (lowest F-actin density) is represented by the rapid and softer viscoelastic compartment while the deep cytoskeleton component (intermediate F-actin density) is represented by the slow and stiffer compartment. Stiffness of both cortical and deep cytoskeleton is significantly decreased when soft confluent monolayer of alveolar epithelial cells replace the rigid plastic substrate while F-actin reconstructions reveal a consistent actin cytoskeleton remodeling observable on both cytoskeleton components.