scholarly journals Macrophage Inflammatory Protein 3α Is Expressed at Inflamed Epithelial Surfaces and Is the Most Potent Chemokine Known in Attracting Langerhans Cell Precursors

2000 ◽  
Vol 192 (5) ◽  
pp. 705-718 ◽  
Author(s):  
Marie-Caroline Dieu-Nosjean ◽  
Catherine Massacrier ◽  
Bernhard Homey ◽  
Béatrice Vanbervliet ◽  
Jean-Jacques Pin ◽  
...  
Keyword(s):  
Hematopoietic Progenitor Cell ◽  
Psoriatic Skin ◽  
Inflammatory Conditions ◽  
Inflammatory Protein ◽  
Inflammatory Stimuli ◽  
Epithelial Immunity ◽  
Factor Α ◽  
Macrophage Inflammatory Protein

Dendritic cells (DCs) form a network comprising different populations that initiate and differentially regulate immune responses. Langerhans cells (LCs) represent a unique population of DCs colonizing epithelium, and we present here observations suggesting that macrophage inflammatory protein (MIP)-3α plays a central role in LC precursor recruitment into the epithelium during inflammation. (a) Among DC populations, MIP-3α was the most potent chemokine inducing the selective migration of in vitro–generated CD34+ hematopoietic progenitor cell–derived LC precursors and skin LCs in accordance with the restricted MIP-3α receptor (CC chemokine receptor 6) expression to these cells. (b) MIP-3α was mainly produced by epithelial cells, and the migration of LC precursors induced by the supernatant of activated skin keratinocytes was completely blocked with an antibody against MIP-3α. (c) In vivo, MIP-3α was selectively produced at sites of inflammation as illustrated in tonsils and lesional psoriatic skin where MIP-3α upregulation appeared associated with an increase in LC turnover. (d) Finally, the secretion of MIP-3α was strongly upregulated by cells of epithelial origin after inflammatory stimuli (interleukin 1β plus tumor necrosis factor α) or T cell signals. Results of this study suggest a major role of MIP-3α in epithelial colonization by LCs under inflammatory conditions and immune disorders, and might open new ways to control epithelial immunity.

scholarly journals Activation of the nuclear factor-κB pathway during postnatal lung inflammation preserves alveolarization by suppressing macrophage inflammatory protein-2

2015 ◽  
Vol 309 (6) ◽  
pp. L593-L604 ◽  
Author(s):  
Yanli Hou ◽  
Min Liu ◽  
Cristiana Husted ◽  
Chihhsin Chen ◽  
Kavitha Thiagarajan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Combined Treatment ◽  
Nuclear Factor Κb ◽  
Inflammatory Stress ◽  
Inflammatory Protein ◽  
Inflammatory Stimuli ◽  
Anti Inflammatory ◽  
Macrophage Inflammatory Protein

A significant portion of lung development is completed postnatally during alveolarization, rendering the immature lung vulnerable to inflammatory stimuli that can disrupt lung structure and function. Although the NF-κB pathway has well-recognized pro-inflammatory functions, novel anti-inflammatory and developmental roles for NF-κB have recently been described. Thus, to determine how NF-κB modulates alveolarization during inflammation, we exposed postnatal day 6 mice to vehicle (PBS), systemic lipopolysaccharide (LPS), or the combination of LPS and the global NF-κB pathway inhibitor BAY 11-7082 (LPS + BAY). LPS impaired alveolarization, decreased lung cell proliferation, and reduced epithelial growth factor expression. BAY exaggerated these detrimental effects of LPS, further suppressing proliferation and disrupting pulmonary angiogenesis, an essential component of alveolarization. The more severe pathology induced by LPS + BAY was associated with marked increases in lung and plasma levels of macrophage inflammatory protein-2 (MIP-2). Experiments using primary neonatal pulmonary endothelial cells (PEC) demonstrated that MIP-2 directly impaired neonatal PEC migration in vitro; and neutralization of MIP-2 in vivo preserved lung cell proliferation and pulmonary angiogenesis and prevented the more severe alveolar disruption induced by the combined treatment of LPS + BAY. Taken together, these studies demonstrate a key anti-inflammatory function of the NF-κB pathway in the early alveolar lung that functions to mitigate the detrimental effects of inflammation on pulmonary angiogenesis and alveolarization. Furthermore, these data suggest that neutralization of MIP-2 may represent a novel therapeutic target that could be beneficial in preserving lung growth in premature infants exposed to inflammatory stress.

scholarly journals Use of 5-fluorouracil to analyze the effect of macrophage inflammatory protein-1 alpha on long-term reconstituting stem cells in vivo

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1497-1504 ◽  
Author(s):  
VF Quesniaux ◽  
GJ Graham ◽  
I Pragnell ◽  
D Donaldson ◽  
SD Wolpe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Inhibitory Effect ◽  
In Vivo Model ◽  
Hematopoietic Progenitors ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Abstract A macrophage-derived inhibitor of early hematopoietic progenitors (colony-forming unit-spleen, CFU-A) called stem cell inhibitor was found to be identical to macrophage inflammatory protein-1 alpha (MIP-1 alpha). We investigated the effect of MIP-1 alpha on the earliest stem cells that sustain long-term hematopoiesis in vivo in a competitive bone marrow repopulation assay. Because long-term reconstituting (LTR) stem cells are normally quiescent, an in vivo model was first developed in which they are triggered to cycle. A first 5-fluorouracil (5-FU) injection was used to eliminate later progenitors, causing the LTR stem cells, which are normally resistant to 5-FU, to enter the cell cycle and become sensitive to a second 5-FU injection administered 5 days later. Human MIP-1 alpha administered from day 0 to 7 was unable to prevent the depletion of the LTR stem cells by the second 5-FU treatment, as observed on day 7 in this model, suggesting that the LTR stem cells were not prevented from being triggered into cycle despite the MIP-1 alpha treatment. However, the MIP-1 alpha protocol used here did substantially decrease the number of more mature hematopoietic progenitors (granulocyte-macrophage colony-forming cells [CFC], burst- forming unit-erythroid, CFCmulti, and preCFCmulti) recovered in the bone marrow shortly after a single 5-FU injection. In vitro, MIP-1 alpha had no inhibitory effect on the ability of these progenitors to form colonies. This study confirms the in vivo inhibitory effect of MIP- 1 alpha on subpopulations of hematopoietic progenitors that are activated in myelodepressed animals. However, MIP-1 alpha had no effect on the long-term reconstituting stem cells in vivo under conditions in which it effectively reduced all later progenitors.

Candida Soluble Cell Wall β-D-Glucan Induces Lung Inflammation in Mice

2007 ◽  
Vol 20 (3) ◽  
pp. 499-508 ◽  
Author(s):  
K. Inoue ◽  
H. Takano ◽  
T. Oda ◽  
R. Yanagisawa ◽  
H. Tamura ◽  
...  
Keyword(s):  
Cell Wall ◽  
Proinflammatory Cytokines ◽  
Lung Inflammation ◽  
Soluble Cell ◽  
Inflammatory Protein ◽  
Enhanced Expression ◽  
Factor Α ◽  
Macrophage Inflammatory Protein ◽  
Necrosis Factor

Bioactivity of cell wall component(s) of fungi has not been fully elucidated, especially in vivo. We isolated Candida soluble beta-D-glucan (CSBG) from Candida albicans (C. albicans). We investigated the effects of airway exposure to CSBG on the immune systems in the airways in mice. CSBG exposure induced neutrophilic and eosinophilic inflammation in the lung, which was concomitant with the increased local expression of proinflammatory cytokines including tumor necrosis factor - α, interleukin (IL)-1 β, IL-6, macrophage inflammatory protein -1 α, macrophage chemoattractant protein -1, RANTES (regulated on activation and normal T cells expressed and secreted), and eotaxin. The lung inflammation with enhanced expression of proinflammatory proteins caused by CSBG was directly related to its structure, since structurally degraded products of CSBG by formic acid induced negligible responses in the lung. CSBG enhanced nuclear localization of phosphorylated signal transducer and activator of transcription (STAT)-6 in the lung. These results suggest that airway exposure to CSBG induces lung inflammation, at least partly, via the enhanced expression of proinflammatory cytokines and the activation of STAT-6 pathway, and can be a proper murine model for fungal lung inflammation.

Acid-induced Lung Injury

2003 ◽  
Vol 99 (6) ◽  
pp. 1323-1332 ◽  
Author(s):  
Lilly Madjdpour ◽  
Sita Kneller ◽  
Christa Booy ◽  
Thomas Pasch ◽  
Ralph C. Schimmer ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Expression Pattern ◽  
Binding Activity ◽  
Pyrrolidine Dithiocarbamate ◽  
Inflammatory Protein ◽  
Nf Kappab ◽  
Macrophage Inflammatory Protein

Background Aspiration of acidic gastric contents leads to acute lung injury and is still one of the most common clinical events associated with acute lung injury. This study was performed to assess acid-induced lung inflammation in vitro and in vivo with respect to the time pattern of activated transcription factor nuclear factor-kappaB (NF-kappaB) and proinflammatory molecules. Methods L2 cells (alveolar epithelial cells) were exposed for various periods to a medium with a pH of 6. In the in vivo model, 1 ml/kg of 0.1 n acidic solution was instilled into the lungs of rats. NF-kappaB binding activity and expression pattern of inflammatory mediators were determined. Blocking studies were performed with the NF-kappaB inhibitor pyrrolidine dithiocarbamate. Results In vitro NF-kappaB binding activity showed a biphasic expression pattern with a first peak at 1 h and a second one at 6-8 h. In acid-injured rat lungs, NF-kappaB binding activity was confirmed in a biphasic manner with a first increase at 0.5-2 h (608 +/- 93% and 500 +/- 15%, respectively, P < 0.05) and a second peak at 8 h (697 +/- 35% increase, P < 0.005). Whole lung mRNA for macrophage inflammatory protein-1beta and macrophage inflammatory protein-2 showed a similar expression pattern, which could explain the biphasic neutrophil recruitment. Intratracheal pyrrolidine dithiocarbamate attenuated lung injury as evidenced by a reduction of neutrophil accumulation and expression of inflammatory mediators. Conclusions These data suggest that NF-kappaB binding activity plays a key role in molecular and cellular events in acid-induced lung injury.

scholarly journals RANTES and macrophage inflammatory protein 1 alpha selectively enhance immunoglobulin (IgE) and IgG4 production by human B cells.

1996 ◽  
Vol 183 (5) ◽  
pp. 2397-2402 ◽  
Author(s):  
H Kimata ◽  
A Yoshida ◽  
C Ishioka ◽  
M Fujimoto ◽  
I Lindley ◽  
...  
Keyword(s):  
B Cells ◽  
Necrosis Factor Alpha ◽  
Platelet Factor ◽  
Human B Cells ◽  
Inflammatory Protein ◽  
Chemotactic Protein ◽  
Macrophage Inflammatory Protein ◽  
Do So

We studied the effects of various chemokines including neutrophil-activating peptide 2 (NAP-2), beta-thromboglobulin (beta-TG), platelet factor 4 (PF-4), melanoma growth stimulating activity (GRO), gamma interferon-induced protein (IP-10), regulated on activation, normal T expressed and secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, and monocyte chemotactic protein 1 (MCP-1) on Immunoglobulin (IgE) and IgG4 production by human B cells. None of these chemokines with or without interleukin (IL-4), anti-CD40 or -CD58 monoclonal antibody (mAb), induced IgE and IgG4 production by B cells from nonatopic donors. However, RANTES and MIP-1 alpha selectively enhanced IgE and IgG4 production induced by IL-4 plus anti-CD40 or -CD58 mAb without affecting production of IgM, IgG1, IgG2, IgG3, IgA1, or IgA2, whereas other chemokines failed to do so. Enhancement of IgE and IgG4 production by RANTES and MIP-1 alpha was specifically blocked by anti-RANTES mAb and anti-MIP-1 alpha antibody (Ab), respectively, whereas anti-IL-5 mAb, anti-IL-6 mAb, anti-IL-10 Ab, anti-IL-13 Ab, and anti-tumor necrosis factor-alpha mAb failed to do so. Purified surface IgE positive (slgE4) and slgG4+ B cells generated either in vitro or in vivo spontaneously produced IgE and IgG4, respectively, whereas sIgE- and sIgG4- B cells failed to do so. RANTES and MIP-1 alpha enhanced spontaneous IgE and IgG4 production in slgE+ and slgG4- B cells, respectively, whereas neither RANTES nor MIP-1 alpha did so in sIgE- or sIgG4- B cells. Purified sIgE4+ and sIgG4+, but not sIgE- or sIgG4- B cells, generated in vitro and in vivo expressed receptors for RANTES and MIP-1 alpha, whereas they failed to express receptors for other chemokines. These findings indicate that RANTES and MIP-1 alpha enhance IgE and IgG4 production by directly stimulating sIgE+ and sIgG4+ B cells.

scholarly journals Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta.

1988 ◽  
Vol 168 (6) ◽  
pp. 2251-2259 ◽  
Author(s):  
B Sherry ◽  
P Tekamp-Olson ◽  
C Gallegos ◽  
D Bauer ◽  
G Davatelis ◽  
...  
Keyword(s):  
Amino Acid ◽  
Inflammatory Responses ◽  
Inflammatory Protein ◽  
Product Comparison ◽  
Synthetic Oligonucleotide Probe ◽  
Terminal Amino ◽  
Macrophage Inflammatory Protein

A number of macrophage-derived mediators have been implicated in the vascular changes of inflammation. We recently reported the isolation of a novel monokine, macrophage inflammatory protein 1 (MIP-1), which causes local inflammatory responses in vivo, and induces superoxide production by neutrophils in vitro. Purified native MIP-1 comprises two peptides with very similar physical characteristics. We report here the resolution of MIP-1 into component peptides by SDS-hydroxylapatite chromatography, and compare the NH2-terminal sequences of the two peptides, now referred to as MIP-1 alpha and MIP-1 beta. A synthetic oligonucleotide probe pool corresponding to the NH2-terminal amino acid sequence of MIP-1 beta was used to isolate a cDNA clone containing its coding sequence. The sequence codes for a 109 amino acid-long polypeptide, of which 69 amino acids correspond to the mature product. Comparison of this MIP-1 beta cDNA with our previously cloned MIP-1 alpha sequence reveals that the MIP-1 peptides, members of a growing family of potential inflammatory mediators, are distinct but highly homologous (58.9% sequence identity) products of different genes.

A cell-surface molecule selectively expressed on murine natural interferon–producing cells that blocks secretion of interferon-alpha

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4201-4206 ◽  
Author(s):  
Amanda Blasius ◽  
William Vermi ◽  
Anne Krug ◽  
Fabio Facchetti ◽  
Marina Cella ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Interleukin 12 ◽  
Surface Molecule ◽  
Adaptive Responses ◽  
Cell Surface Molecule ◽  
Peripheral Tissues ◽  
Inflammatory Conditions ◽  
Inflammatory Stimuli

Abstract Natural interferon (IFN)-producing cells (IPCs) recognize certain viruses and DNA containing deoxycytidylate-phosphatedeoxyguanylate (CpG) motifs through the toll-like receptor (TLR) 9, resulting in secretion of IFN-α, interleukin 12 (IL-12), and proinflammatory chemokines. Human IPCs are found mainly in inflamed lymph nodes, where they are presumably recruited from the blood to activate both innate and adaptive responses to microbial infections. Demonstrating IPC recruitment and function in murine infection models has been difficult because multiple antibodies are required to distinguish IPCs from other immune cells and very few IPCs can be recovered from lymph nodes. Here we describe a monoclonal antibody (mAb) that exclusively detects murine IPCs in all lymphoid organs under both normal and inflammatory conditions. Using this antibody, we demonstrate that IPCs are normally present in the T-cell zone of lymph nodes and spleen and that inoculation of peripheral tissues with inflammatory stimuli triggers recruitment of IPC into sentinel lymph nodes, whether the stimuli are able to directly stimulate IPCs through TLR or not. Remarkably, we show that incubation of IPCs with the antibody in vitro or administration of the antibody in vivo dramatically reduce secretion of IFN-α in response to CpG DNA without causing IPC depletion. Thus, the antibody identifies an IPC-specific surface molecule that, when engaged, inhibits IFN-α secretion. (Blood. 2004;103:4201-4206)

Macrophage Inflammatory Protein (MIP)-3α/CCL20 and Its Receptor CCR6 Are Overexpressed in the Bone Microenvironment and Involved in Osteoclast Formation in Multiple Myeloma Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3510-3510 ◽  
Author(s):  
Nicola Giuliani ◽  
Gina Lisignoli ◽  
Sara Tagliaferri ◽  
Mirca Lazzaretti ◽  
Francesca Morandi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Osteoclast Formation ◽  
Bone Lesions ◽  
Mrna Levels ◽  
Bone Microenvironment ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Abstract Osteoclast (OC) activation in multiple myeloma (MM) is primarily due to the imbalance of the critical osteoclastogenic system RANKL/OPG in the bone microenvironment. Recent evidences indicate that chemokines, small chemoattractant proteins involved in cancer cell homing, may contribute to osteoclast formation and activation. However, whereas the role of the chemokine macrophage inflammatory protein (MIP)-1α in MM-induced OC activation is well established, the involvement of other chemokines is not known. In this study, we evaluated the potential role of MIP-3α/CCL20 and its receptor CCR6 in the pathophysiology of OC formation and osteolytic lesions in MM. First the effect of MIP-3α/CCL20 on in vitro osteoclast formation by peripheral monocytes was evaluated. (MIP)-3α/CCL20 significantly increased both the number of multinucleated TRAP+ OCs and RANK+ OC progenitor cells in presence of RANKL. In addition we found that (MIP)-3α/CCL20 increases RANKL mRNA levels in both human osteoblastic (OB) and bone marrow (BM) osteoprogenitor cells (preOB). Following, the potential production of (MIP)-3α/CCL20 by human MM cell lines (HMCLs) and fresh purified CD138+ MM cells was also checked. Significant levels of (MIP)-3α/CCL20 were detected in one out of nine HMCLs tested and in about 10% of purified MM cells by ELISA and immunohystochemistry. On the other hand we found that MM cells up-regulated (MIP)-3α/CCL20 secretion, in OB/PreOB cells and in OCs as well as its receptor CCR6 in OCs in co-culture systems in presence of a transwell insert. Among potential soluble factors involved in the up-regulation of MIP-3α/CCL20 by MM cells we found that IL-1β and TNFα together stimulate MIP-3α/CCL20 production in both OB and PreOB. The role of MIP-3α/CCL20 in OC activation by MM cells was finally demonstrated by finding that both blocking anti-(MIP)-3α/CCL20 and anti-CCR6 Abs. but not anti-IgG control significantly decreased OC formation induced by the conditioned medium of MM cells co-cultured with OB and OC, respectively. This chemokine system was further studied in vivo in MM patients. MIP-3α/CCL20 levels were detected in the BM plasma of MGUS subjects (n°=16) and in MM (n°=52) patients at the diagnosis in relationship with the presence of bone lesions (osteolytic n°= 32; non-osteolytic: n°=20). Significant higher MIP-3α/CCL20 levels were detected in MM patients vs. MGUS (mean ± SD: 51.9±2 vs. 21±3 pg/mL; p=0.01) and in MM osteolytic patients vs. non-osteolytic ones (mean ± SD: 70.8±5.9 vs. 13.8±1.1 pg/mL; p=0.001). Interestingly, no significant differences were observed between MGUS and non-osteolytic MM patients. By immunohystochemistry performed on BM biopsies, we consistently found that MIP-3α/CCL20 was over-expressed in OBs in osteolytic MM patients as compared to non-osteolytic ones. In addition we found that OCs showed a strong CCR6 staining in the areas with an increased number of OCs. In conclusion our data indicate that (MIP)-3α/CCL20 its receptor CCR6 are up-regulated in bone microenvironment by MM cells and involved in osteoclast formation and bone lesions in MM patients.

scholarly journals Novel Rifampicin and Indocyanine Green Co-Loaded Perfluorocarbon Nanodroplets Provide Effective In Vivo Photo–Chemo–Probiotic Antimicrobility against Pathogen of Acne Vulgaris Cutibacterium acnes

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1095
Author(s):  
Kuang-Hung Hsiao ◽  
Chun-Ming Huang ◽  
Yu-Hsiang Lee
Keyword(s):  
Indocyanine Green ◽  
Staphylococcus Epidermidis ◽  
Near Infrared ◽  
Acne Vulgaris ◽  
Inhibition Zone ◽  
Inflammatory Protein ◽  
Cutibacterium Acnes ◽  
Macrophage Inflammatory Protein

Acne vulgaris is one of the most prevalent dermatological diseases among adolescents and is often associated with overgrowth of Cutibacterium acnes (C. acnes) in the pilosebaceous units. In this study, we aimed to develop novel rifampicin (RIF) and indocyanine green (ICG) co-loaded perfluorocarbon nanodroplets named RIPNDs which can simultaneously provide photo-, chemo-, and probiotic-antimicrobility, and explore their efficacy in treatment of C. acnes in vitro and in vivo. The RIPNDs were first characterized as being spherical in shape, with a size of 238.6 ± 7.51 nm and surface charge of −22.3 ± 3.5 mV. Then, the optimal dosages of Staphylococcus epidermidis–produced fermentation product medium (FPM) and RIPND were determined as 25% (v/v) and [RIF]/[ICG] = 3.8/20 μM, respectively, based on the analyses of inhibition zone and cytotoxicity in vitro. Through the in vivo study using C. acnes–inoculated mice, our data showed that the group treated with FPM followed by RIPNDs + near infrared (NIR) irradiation obtained the least granulocytes/macrophage-inflammatory protein 2 expression level in the epidermis, and showed a significantly lower microbial colony population compared to the groups treated with equal amount of RIF, FPM, RIPNDs, and/or combination of the above ± NIR. These results indicated that the RIPND-mediated photo–chemo–probiotic therapeutics was indeed able to rapidly suppress inflammatory response of the skin and provide a robust antibacterial effect against C. acnes with limited use of antibiotics. Taken altogether, we anticipate that the RIPND is highly potential for use in the clinical treatment of acne vulgaris.

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