In the original version of Figure 2B, two of the patient identifiers were incorrectly noted. OS-11 and OS-12 were listed twice. The second instances should have been labeled as CID-11 and CID-12, respectively. The correct figure panel is below.The authors regret the error.

Macrophages acquire their capacity for efficient phagocytosis of apoptotic cells during their differentiation from monocytes. The peroxisome proliferator-activated receptor gamma (PPARc) is highly up-regulated during this maturation program. We report that addition of PPARc antagonist during differentiation of human monocytes to macrophages significantly reduced the capacity of macrophages to engulf apoptotic neutrophils, but did not influence phagocytosis of opsonized bacteria. Macrophagespecific deletion of PPARc in mice also resulted in decreased uptake of apoptotic cells. The antagonist acted in a dose-dependent manner during the differentiation of human macrophages and could also reverse the previously observed augmentation of phagocytosis by glucocorticoids. Blocking activation of PPARc led to down-regulation of molecular elements (CD36, AXL, TG2 and PTX3) of the engulfment process. Inhibition of PPARc-dependent gene expression did not block the anti-inflammatory effect of apoptotic neutrophils or synthetic glucocorticoid, but significantly decreased production of IL-10 induced by LPS. Our results suggest that during differentiation of macrophages natural ligands of PPARc are formed, regulating the expression of genes responsible for effective clearance of apoptotic cells and macrophage-mediated inflammatory responses.

Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2 ؊/؊ mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2 ؊/؊ mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil. ( IntroductionTransglutaminases are a family of Ca 2ϩ -dependent enzymes that can mediate covalent cross-linking of proteins by forming isodipeptide bonds between glutamines and the ⑀-amino groups of lysine residues (transglutamylation). 1 Several distinct transglutaminases have been described in vertebrates. Among them, TG2, also referred to as tissue transglutaminase, is a multifunctional protein and the only member of the transglutaminase family expressed in a wide variety of tissues and cell types. 2 In addition to cross-linking protein, TG2 can modify proteins by amine incorporation, deamination, and by acting as an isopeptidase in a Ca 2ϩ -dependent manner. 3 Although TG2 cross-links several intracellular and extracellular proteins, the biologic significance of its enzymatic functions is still far from being completely understood. It has been shown in several experimental models that TG2 facilitates apoptosis and clearance of dead cells in response to stimuli that result in its increased expression and activation of transamidating activity. 3 TG2 is also known as a cell surface adhesion mediator. Integrin-bound TG2 on the cell surface provides a binding site for fibronectin and facilitates adhesion and spreading of cells. 4,5 It plays a significant role in wound healing and angiogenesis, as well as in the assembly, remodeling, and stabilization of the extracellular matrix in various tissues. 6,7 The GTP-binding form of TG2, which mediates intracellular signaling by ␣1B and ␣1D adrenergic receptors, has a signaling function apart from its transamidating activity. 8,9 Data suggest that TG2 d...