Enhancement of macrophage phagocytosis upon iC3b deposition on apoptotic cells

Nonphlogistic Clearance of Late Apoptotic Neutrophils by Macrophages: Efficient Phagocytosis Independent of β2 Integrins

“…Nevertheless, when such cells were interacted in the absence of added serum with human monocyte-derived M , no defect in phagocytosis of apoptotic neutrophils was observed despite functionally validated Ab blockade of M , CR1, CR3, and CR4 receptors (38), nor was any obvious defect in phagocytosis exhibited by monocyte-derived M prepared from a patient with severe congenital ␤ 2 deficiency (40). However, our findings must be set against 1) growing evidence that the first component of complement, C1q, could bridge apoptotic cells to phagocytes in a manner similar to that proposed for TSP1 (41,42), and 2) compelling data suggesting that M receptors for opsonic complement fragments could be important in amplifying efficient phagocytosis of dying cells (17,29). Nevertheless, it is notable that these latter reports have either used mixed populations of dying cells, including cells in secondary necrosis (17), or have used assays of interaction with M that include a large tethering element (29) rather than our own extensively validated assay of completed phagocytosis.…”

“…However, our findings must be set against 1) growing evidence that the first component of complement, C1q, could bridge apoptotic cells to phagocytes in a manner similar to that proposed for TSP1 (41,42), and 2) compelling data suggesting that M receptors for opsonic complement fragments could be important in amplifying efficient phagocytosis of dying cells (17,29). Nevertheless, it is notable that these latter reports have either used mixed populations of dying cells, including cells in secondary necrosis (17), or have used assays of interaction with M that include a large tethering element (29) rather than our own extensively validated assay of completed phagocytosis. Further studies will be needed to resolve the importance of complement components in removal of neutrophils at various stages of the apoptotic death program.…”

“…14 -16 for reviews) have been implicated in vitro. This complexity may reflect the fact that studies have frequently involved administration to phagocytes of "meals" consisting of heterogeneous populations containing cells at various stages of the death program, including secondary necrosis (17). By contrast, human neutrophils undergoing constitutive apoptosis during overnight culture contain a mixture of histologically normal neutrophils (not ingested by phagocytes) and intact cells that exclude trypan blue and propidium iodide (PI) 3 and exhibit classical morphologic features of early apoptosis (3).…”

“…However, equally strong candidate phagocyte receptors were those of the ␤ 2 integrin family that bind opsonic complement fragments, type 3 complement receptor (CR3; ␣ m ␤ 2 or CD11b/CD18) and CR4 (␣ x ␤ 2 or CD11c/ CD18). Not only does ligation of these receptors fail to stimulate the release of inflammatory mediators from M s (27,28), but there is also evidence that they can bind, via opsonic complement fragments, populations of dying cells (17,29). Furthermore, ␤ 2 integrins can also bind denatured proteins (30), which might be exposed by late apoptotic cells.…”

Differential mechanisms of microparticle transfer toB cells and monocytes: anti‐inflammatory propertiesof microparticles

“…Microparticles exposed to serum are able to activate complement, resulting in a deposition of iC3b on their surface. It has previously been shown for apoptotic cells that complement activation plays an important role for their uptake by macrophages and immature dendritic cells [27][28][29]. Phosphatidylserine on apoptotic cells is at least partially involved in the activation of complement and contributes to the deposition of complement components like iC3b on the membrane surface [27,30,31].…”