Macrophages increase microparticle uptake by enterocyte-like Caco-2 cell monolayers.

Area of Science:

• Cell Biology
• Drug Delivery Systems
• Toxicology

Background:

• Caco-2 cells form an enterocyte-like monolayer, serving as a model for small intestinal studies.
• This model is used to investigate drug delivery systems and the uptake of particulate environmental pollutants.
• Previous studies reported decreased Caco-2 transepithelial resistance upon macrophage exposure.

Purpose of the Study:

• To determine if decreased Caco-2 transepithelial resistance correlates with increased microparticle uptake when macrophages are present.
• To investigate the impact of macrophage phagocytosis on particle removal from the subepithelial compartment.
• To analyze the structural and functional changes in Caco-2 cells induced by co-culture with macrophages.

Main Methods:

• Caco-2 cells were cultured as a monoculture for 21 days on insert membranes.
• A compartmentalized model was used with Caco-2 cells and THP-1-derived macrophages.
• Cells were exposed apically to 2 μm latex particles, and parameters like transepithelial resistance, cytokine levels, and cell morphology were measured.

Main Results:

• Subepithelial particle numbers significantly increased in the Caco-2/macrophage model, with most particles associated with macrophages.
• Macrophage presence led to decreased transepithelial resistance, disorganized cell structure, and altered junctional protein localization.
• Exposure to macrophage-conditioned medium induced fewer changes compared to the direct co-culture model.

Conclusions:

• Co-culturing Caco-2 cells with underlying macrophages results in a compromised epithelial barrier.
• This model demonstrates enhanced microparticle uptake, with macrophages playing a key role in subepithelial particle accumulation.
• Findings highlight the importance of immune cell interactions in modulating intestinal barrier function and particle transport.