Journal: iScience

Article Title: A LTB 4 /CD11b self-amplifying loop drives pyogranuloma formation in chronic granulomatous disease

doi: 10.1016/j.isci.2024.109589

Figure Lengend Snippet: LTB 4 mediates the ex vivo aggregation of peritoneal lavage cells from zymosan-treated CGD mice via the aggregation of neutrophils (A and B) PL cells were harvested at 6 h post-zymosan, plated, cultured for 24 h with either vehicle or LTB 4 receptor antagonists together (A) or individually (B), fixed, stained and imaged as in Figure 1 C. Four images were analyzed per coverslip using Imaris software to define the number of aggregates within the image and the average size of the aggregates detected. N = 4–5 mice, from 2 to 5 experiments. p values were determined by paired t-test. ∗p < 0.05, ∗∗p < 0.01. (C) LTB 4 in conditioned media was measured by ELISA following 24-h culture of 6-h (left) and 20-h (right) PL cells. N = 8–9 samples, from 3 experiments. p values were determined by multiple t-tests. ∗∗∗∗p < 0.0001. (D) PL cells were harvested at 20 h post-zymosan, plated, cultured for 24 h with either vehicle or both LTB 4 receptor antagonists, fixed, stained and imaged as in Figure 1 C. Four images were analyzed per coverslip using Imaris software to define the number of aggregates within the image and the average size of the aggregates detected. N = 5 mice, from 5 experiments. p values were determined by paired t-test. ∗p < 0.05. (E) Labeled MoMacs from WT and BLT1 −/− mice were recruited to aggregates initiated by 6-h CGD PL cells and were quantified as in Figure 2 . N = 3 mice, from 3 experiments. p values were determined by multiple t-tests. (F) TNFα, G-CSF, CXCL1, CXCL2, IL-6, CCL2, CCL3, and CCL4 were measured by multiplex or by ELISA following 24-h culture of 6-h or 20-h CGD PL cells cultured in the presence of vehicle or BLT1 and BLT2 antagonists. N = 6–9 samples, from 3 experiments. p values were determined by multiple t-tests. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001.

Article Snippet: Anti-CCL2 , BioXcell , Clone 2H5.

Techniques: Ex Vivo, Cell Culture, Staining, Software, Enzyme-linked Immunosorbent Assay, Labeling, Multiplex Assay

Journal: iScience

Article Title: A LTB 4 /CD11b self-amplifying loop drives pyogranuloma formation in chronic granulomatous disease

doi: 10.1016/j.isci.2024.109589

Figure Lengend Snippet: Neither CCL2, CCL3, CCL4 nor LTB 4 mediate the recruitment of MoMacs to CGD aggregates (A) Levels of CCL2, CCL3, and CCL4 in conditioned media after 24-h culture of 20-h peritoneal lavage cells were measured by multiplex assay. N = 9 samples, from 3 experiments. p values were determined by t-test. ∗∗p < 0.01, ∗∗∗p < 0.001. (B) Recruitment of labeled WT and BLT1 −/− enriched MoMacs into CGD 6-h PL neutrophil aggregates in the presence of anti-CCL2/3/4 antibodies was assessed and analyzed as in Figure 2 . Dotted line represents WT MoMacs found in the aggregates after 18 h in culture in the absence of the antibodies. N = 3 mice, from 3 experiments. p values were determined by multiple t-tests.

Article Snippet: Anti-CCL2 , BioXcell , Clone 2H5.

Techniques: Multiplex Assay, Labeling

Journal: iScience

Article Title: A LTB 4 /CD11b self-amplifying loop drives pyogranuloma formation in chronic granulomatous disease

doi: 10.1016/j.isci.2024.109589

Figure Lengend Snippet: CD11b expression on neutrophils is elevated in CGD, lowered by LTB 4 receptor antagonists, and mediates the aggregation of peritoneal lavage cells ex vivo (A) CD11b surface expression was measured by flow cytometry on 6-h PL neutrophils (left) and 20-h PL neutrophils and MoMacs (right) post-zymosan. N = 4–8 mice, from 2 to 3 experiments. p values were determined by multiple t-tests. ∗∗∗p < 0.001. (B) CD11b expression was measured on 20-h PL neutrophils after 24 h culture with vehicle or the LTB4 receptor antagonists. N = 4 mice, from 3 experiments. p values were determined by paired t-test. ∗p < 0.05. (C) CGD PL cells were harvested at 20 h and 6 h post-zymosan and allowed to aggregate with or without blocking anti-CD11b antibody and analyzed as in Figures 3 B and 3C. N = 3 mice, from 3 experiments. p values were determined by paired t-test. ∗p < 0.05. (D) Recruitment of WT and CD11b −/− (left) and CGD and CD11b −/− CGD (right) enriched MoMacs into CGD 6-h PL neutrophil aggregates was performed and analyzed as in Figure 2 . N = 3–4 mice, from 3 to 4 experiments. p values were determined by multiple t-tests. (E) Levels of LTB 4 in cell culture supernatants after 24-h culture of 6-h (left) and 20-h (right) PL cells as measured by ELISA. N = 6 samples, from 2 experiments. p values were determined by multiple t-tests. ∗∗∗p < 0.001. (F) TNFα, G-CSF, CXCL1, CXCL2, IL-6, CCL2, CCL3, and CCL4 were measured by multiplex or by ELISA following 24-h culture of 6-h or 20-h CGD or CD11b −/− CGD cells. N = 9 samples, from 3 experiments. p values were determined by multiple t-tests. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001.

Article Snippet: Anti-CCL2 , BioXcell , Clone 2H5.

Techniques: Expressing, Ex Vivo, Flow Cytometry, Blocking Assay, Cell Culture, Enzyme-linked Immunosorbent Assay, Multiplex Assay

Journal: iScience

Article Title: A LTB 4 /CD11b self-amplifying loop drives pyogranuloma formation in chronic granulomatous disease

doi: 10.1016/j.isci.2024.109589

Figure Lengend Snippet:

Article Snippet: Anti-CCL2 , BioXcell , Clone 2H5.

Techniques: Recombinant, Sequencing, Enzyme-linked Immunosorbent Assay, Software

Journal:

Article Title: Chemokines and chemokine receptors: new insights into cancer-related inflammation

doi: 10.1016/j.molmed.2010.01.003

Figure Lengend Snippet: Summary of the chemokines and chemokine receptors in cancer *

Article Snippet: Phase I/II Solid tumors CT MSX-122 Small molecule inhibitor Metastatix Inc Phase I suspended Solid tumors 66 CCR4 KW0761 Antibody Kyowa Hakko Kogyo Co Phase II Adult T-cell leukemia and lymhoma, peripheral T-cell leukemia 65 , CT CCR5 Sch-C Small molecule inhibitor Schering-Plough Phase I Cancer 69 CCR9 CCX282 Small molecule inhibitor ChemoCentryx Phase III Crohn’s disease 67 , 68 , 73 CCL2 CNTO 888 Antibody Centocor Phase I Solid tumors 65 MLN1202 Antibody Millenium Phase II Bone metastasis CT Open in a separate window * CT: clinicaltrials.gov Survey of the clinical trials targeting chemokines in cancer In the short term, novel approaches are likely to involve drugs that have already been tested in preclinical settings.

Techniques:

Journal:

Article Title: Chemokines and chemokine receptors: new insights into cancer-related inflammation

doi: 10.1016/j.molmed.2010.01.003

Figure Lengend Snippet: Chemokines can modulate cancer cell proliferation, apoptosis, senescence and invasion and participate in tumor angiogenesis as well as leukocyte infiltration. Cancer cells are shown in red. Recent findings suggest that CXCR7 could be involved in the control of proliferation. CXCR7 could also inhibit apoptosis, whereas CCL2 impedes autophagic death. Senescence is also tightly regulated by CXCR2 and its ligands CXCL1 and CXCL8. Decoy receptors such as DARC and D6 could regulate angiogenesis negatively. Other chemokines such as CXCL1, CXCL8 and their receptor CXCR2 promote angiogenesis. CXCL1 is induced by prostaglandin E2 (PGE2), whereas CXCL8 is negatively regulated by prolylhydroxylase 2 (PHD2). Homing of cancer cells to specific metastatic sites is tightly controlled by chemokines CXCL1,8, 12, CCL5, CCL19, 21, 25, 27 and chemokine receptors CCR5, 7, 9, 10 and CX3CR1. CXCL12 levels are induced by Src (a non-receptor cytoplasmic tyrosine kinase) and in turn can modulate metastasis. CCR7, whose expression is controlled by Notch1 and interstitial flow, plays an active role in metastasis. Several reports have indicated the central role played by TGFβ, which can induce CXCL12 expression, but are also induces CCL2, 5, CXCR2 and CXCR4 expression. In turn, these chemokines and chemokine receptors promote inflammatory cell infiltration. By contrast, TGFβ down-regulates CXCL1, 5, 8, CCL9 and CCR1 levels, which acts to further modulate leukocyte infiltration.

Article Snippet: Phase I/II Solid tumors CT MSX-122 Small molecule inhibitor Metastatix Inc Phase I suspended Solid tumors 66 CCR4 KW0761 Antibody Kyowa Hakko Kogyo Co Phase II Adult T-cell leukemia and lymhoma, peripheral T-cell leukemia 65 , CT CCR5 Sch-C Small molecule inhibitor Schering-Plough Phase I Cancer 69 CCR9 CCX282 Small molecule inhibitor ChemoCentryx Phase III Crohn’s disease 67 , 68 , 73 CCL2 CNTO 888 Antibody Centocor Phase I Solid tumors 65 MLN1202 Antibody Millenium Phase II Bone metastasis CT Open in a separate window * CT: clinicaltrials.gov Survey of the clinical trials targeting chemokines in cancer In the short term, novel approaches are likely to involve drugs that have already been tested in preclinical settings.

Techniques: Control, Expressing

Journal:

Article Title: Chemokines and chemokine receptors: new insights into cancer-related inflammation

doi: 10.1016/j.molmed.2010.01.003

Figure Lengend Snippet: Survey of the clinical trials targeting chemokines in cancer

Article Snippet: Phase I/II Solid tumors CT MSX-122 Small molecule inhibitor Metastatix Inc Phase I suspended Solid tumors 66 CCR4 KW0761 Antibody Kyowa Hakko Kogyo Co Phase II Adult T-cell leukemia and lymhoma, peripheral T-cell leukemia 65 , CT CCR5 Sch-C Small molecule inhibitor Schering-Plough Phase I Cancer 69 CCR9 CCX282 Small molecule inhibitor ChemoCentryx Phase III Crohn’s disease 67 , 68 , 73 CCL2 CNTO 888 Antibody Centocor Phase I Solid tumors 65 MLN1202 Antibody Millenium Phase II Bone metastasis CT Open in a separate window * CT: clinicaltrials.gov Survey of the clinical trials targeting chemokines in cancer In the short term, novel approaches are likely to involve drugs that have already been tested in preclinical settings.

Techniques: Clinical Proteomics