Neutrophils are potent immune effectors against bacterial infections. Macrophages are important in infections as effectors and regulators, but their exact roles, phenotypic characterization and their relation to neutrophils is incompletely understood. Here we report in a model of bacterial urinary tract infection, one of the most prevalent bacterial infections that tissue-resident Ly6C− macrophages recruited circulating neutrophils and inflammatory Ly6C+ macrophages through chemokines. Neutrophils were primarily recruited through ligands of the chemokine receptor CXCR2, in particular by CXCL1 and less by macrophage migration inhibitory factor (MIF), but not through CXCL5 and CXCL2. Neutrophils, but not Ly6C+ macrophages, cleared the bacteria by phagocytosis. Ly6C+ macrophages instead performed a regulatory function: in response to the infection, they produced the cytokine tumor necrosis factor (TNF), which in turn caused the resident macrophages to secrete CXCL2. This chemokine induced the secretion of matrix metalloproteinase-9 (MMP-9) in neutrophils and allowed these cells to degrade the uroepithelial basement membrane, in order to enter the uroepithelium, the mucosal interface from where the bacteria invade the bladder. Thus, the phagocyte response against bacteria is a highly coordinated event, in which Ly6C− macrophages act as sentinels and Ly6C+ macrophages as innate helper cells. In analogy with T helper cells (Th), we propose to name these helper macrophages (Ph) as they provide a second signal on whether to unleash the principal effector phagocytes, the neutrophils. This cellular triage may prevent ‘false-positive’ immune responses. The role of TNF as innate ‘licensing’ factor contributes to its central role in antibacterial immunity.
Oxidovanadium(IV) complexes of 2-(2Ј-pyridyl)-1,10-phenanthroline (pyphen), viz. [VO(pyphen)(acac)](ClO 4 ) (1), [VO(pyphen)(anacac)](ClO 4 ) (2) and [VO(pyphen)(cur)]-(ClO 4 ) (3), where acac is acetylacetonate (in 1), anacac is anthracenylacetylacetonate (in 2) and cur is curcumin monoanion (in 3) were synthesized, characterized and their photo-induced DNA cleavage activities and photo-cytotoxicities studied. The complexes are 1:1 electrolytes in DMF. The one-electron paramagnetic complexes show a d-d band near 760 nm in DMF. Complexes 2 and 3 are blue and green emissive, respectively, in DMSO. The complexes exhibit irreversible V IV /V III reductive responses near -1.1 V and V V /V IV oxidative responses near 0.85 V vs. SCE in DMF-0.1 M TBAP. Complexes 2 and 3 display significant and selective photo-[a] 448 well with those of the well established PDT drug Photofrin ® .
An oxovanadium(IV) vitamin-B6 Schiff base complex, viz. [VO(HL)(acdppz)]Cl, having (acridinyl)dipyridophenazine (acdppz) shows specific localization to endoplasmic reticulum (ER) and remarkable apoptotic photocytotoxicity in visible light (400-700 nm) in HeLa and MCF-7 cancer cells (IC50 < 0.6 μM) while being non-toxic in the dark and to MCF-10A normal cells (IC50 > 40 μM).
BODIPY-appended copper(ii) complexes of curcumin show a remarkable PDT effect in visible light in HeLa cells via apoptosis with mitochondrial localization.
BODIPY-appended copper(ii) complexes are for cellular imaging and visible light-induced remarkable PDT activity in HeLa/MCF-7 cells with 1O2-mediated cellular apoptosis.
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