Phagocytosis of apoptotic eosinophils but not neutrophils by bronchial epithelial cells

Abstract

Summary Background We have previously demonstrated that human bronchial epithelial cells engulf apoptotic eosinophils. Objectives To compare and contrast the phagocytic capabilities of monocyte‐derived macrophage and primary airway epithelial cells for apoptotic granulocytes. Results Here we compared phagocytosis of human apoptotic eosinophils and neutrophils by small and large airway epithelial cells (SAEC and LAEC) and monocyte‐derived macrophages. Confocal microscopy of F‐actin staining and scanning and transmission electron microscopy revealed phagocytic cup formation around apoptotic eosinophils by airway epithelial cells (AEC) membranes with evidence of their digestion. Resting and cytokine‐stimulated AEC did not recognize and ingest apoptotic neutrophils. The latter were phagocytosed by macrophages that exhibited greater ingestion of and higher capacity for, apoptotic eosinophils over apoptotic neutrophils. Cytochalasin D completely abolished uptake of apoptotic eosinophils by SAEC, LAEC or macrophage monolayers. Ligation of epithelial cell CD44 receptors for 24 h increased phagocytosis of apoptotic eosinophils by SAEC and LAEC with a potency comparable with that of IL‐1. Phagocytosis was a specific receptor‐mediated process involving integrin‐ (αvβ3, αvβ5, CD36), phosphatidylserine receptor‐ and lectin‐dependent mechanisms. No significant differences were observed in avarice for apoptotic eosinophils by SAEC or LAEC either resting, CD44 monoclonal antibodies‐ or cytokine‐ stimulated, or in their usage and expression of recognition receptors. Conclusion These findings further suggest and define an important role for the bronchial epithelium in the selective removal of apoptotic eosinophils from the airways in asthma.

CD44 is a phagocytic receptor

“…25 CD44 has also been implicated in clearance of apoptotic cells 17 and, as in bacterial phagocytosis, there is evidence that CD44 may function as a coreceptor during this process. For example, ligation of CD44 on macrophages or on airway epithelial cells increases the ensuing uptake of apoptotic neutrophils 19,21 and eosinophils, 20 respectively. During internalization of apoptotic cells there are several potential ligands on the surface of the apoptotic prey that could bind CD44 on the phagocyte plasma membrane, including hyaluronan and CD44 itself.…”

“…16 Observations also point to a role for CD44 in binding, ingestion (phagocytosis), and clearance of apoptotic cells 17 and microbial pathogens. 18 With respect to clearance of apoptotic cells, direct antibody ligation of CD44 on macrophages 19 or on airway epithelial cells 20 enhanced subsequent uptake of apoptotic neutrophils and eosinophils, respectively, suggesting a costimulatory function for the receptor. However, ensuing reports have suggested that some of these effects may be attributed to the Fc portion of the macrophage-bound anti-CD44 antibody interacting with the Fc␥-receptor on the leukocytes.…”

P2X7 Receptor-mediated Scavenger Activity of Mononuclear Phagocytes toward Non-opsonized Particles and Apoptotic Cells Is Inhibited by Serum Glycoproteins but Remains Active in Cerebrospinal Fluid

“…The highest expression of P2X7 receptors is on professional phagocytes of monocyte/macrophage lineage including microglia (10), but P2X7 also has ubiquitous distribution, and other cell types (e.g. epithelial and both mature and progenitor neuronal cells) are able to recognize and engulf apoptotic cells at slower rates (11)(12)(13). Apart from certain complement components (14), physiological regulators in the process of non-inflammatory removal of apoptotic cells have yet to be identified.…”

Roles of the Innate Immune System in Mammary Gland Remodeling During Involution

“…Several other types of epithelial cells have been shown to be capable of phagocytosis in vitro. Human alveolar and airway epithelial cells can engulf apoptotic eosinophils [21][22][23], suggesting that epithelial-mediated phagocytosis may help to accelerate the resolution of inflammation in the lung.…”