Human Alveolar Macrophage-derived Chemotactic Factor for Neutrophils

Hunninghake, Gary W.; Gadek, James E.; Fales, Henry M.; Crystal, Ronald G.

doi:10.1172/jci109878

Cited by 216 publications

(59 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ischemic wounds overexpressed genes encoding neutrophil chemotactic factors. Human alveolar macrophage-derived chemotactic factor (AMCF) for neutrophils amplify the inflammatory processes seen in many acute and chronic diseases (25). CXCL2 or macrophage inflammatory protein 2-alpha (MIP2-␣), another chemotactic factor for polymorphonuclear leukocytes, was also overexpressed in ischemic wounds as was CCR1, the Fig.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a preclinical model of chronic ischemic wound

Roy

Biswas

Khanna

et al. 2009

Physiological Genomics

111

View full text Add to dashboard Cite

Chronic ischemic wounds presenting at wound clinics are heterogeneous with respect to etiology, age of the wound, and other factors complicating wound healing. In addition, there are ethical challenges associated with collecting repeated biopsies from a patient to develop an understanding of the temporal dynamics of the mechanisms underlying chronic wounds. The need for a preclinical model of ischemic wound is therefore compelling. The porcine model is widely accepted as an excellent preclinical model for human wounds. A full-thickness bipedicle flap approach was adopted to cause skin ischemia. Closure of excisional wounds placed on ischemic tissue was severely impaired resulting in chronic wounds. Histologically, ischemic wounds suffered from impaired re-epithelialization, delayed macrophage recruitment and poorer endothelial cell abundance and organization. Compared with the pair-matched nonischemic wound, unique aspects of the ischemic wound biology were examined on days 3, 7, 14, and 28 by systematic screening of the wound tissue transcriptome using high-density porcine GeneChips. Ischemia markedly potentiated the expression of arginase-1, a cytosolic enzyme that metabolizes the precursor of nitric oxide l-arginine. Ischemia also induced the SOD2 in the wound tissue perhaps as survival response of the challenged tissue. Human chronic wounds also demonstrated elevated expression of SOD2 and arginase-1. This study provides a thorough database that may serve as a valuable reference tool to develop novel hypotheses aiming to elucidate the biology of ischemic chronic wounds in a preclinical setting.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of a preclinical model of chronic ischemic wound

Roy

Biswas

Khanna

et al. 2009

Physiological Genomics

111

View full text Add to dashboard Cite

show abstract

“…Sequestration of PMN within the lung is characteristic of acute and chronic lung injury, including acute chest syndrome in SCD patients. Most of the previous studies have focused on human alveolar macrophage as a primary source of this chemotactic activity (38) and proinflammatory cytokine-mediated expression of IL-8 in endothelial cells (39). In this study, we examined the molecular mechanism by which hypoxia up-regulates the expression of CXC chemokine IL-8 in human vascular endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

A Novel Role of Hypoxia-Inducible Factor in Cobalt Chloride- and Hypoxia-Mediated Expression of IL-8 Chemokine in Human Endothelial Cells

Kim¹,

Rajagopal²,

Gonsalves³

et al. 2006

The Journal of Immunology

169

123

View full text Add to dashboard Cite

Tissue hypoxemia is common in several pathological diseases, including vaso-occlusion in sickle cell disease and myocardial infarction. One finds increased presence of leukocytes during lung injury and at sites of inflammation in vascular endothelium. In this study, we used human pulmonary microvascular endothelial cells and human dermal microvascular endothelial immortalized cell line to delineate the cellular signaling mechanism of hypoxia- and CoCl2 (a mimetic of hypoxia)-induced IL-8 expression, and the latter’s role in chemotaxis of polmorphonuclear neutrophils. We show that hypoxia- and CoCl2-induced IL-8 mRNA and protein expression involved activation of PI3K/Akt and p38 MAPK, but not MEK kinase. Analysis of some transcription factors associated with IL-8 promoter revealed that hypoxia and CoCl2 increased DNA-binding activity of hypoxia-inducible factor-1α (HIF-1α), NF-κB, and AP-1. In addition, we show that hypoxia- and CoCl2-induced IL-8 expression requires activation of HIF as demonstrated by the following: 1) EMSA; 2) transfection studies with IL-8 promoter reporter constructs with mutation in HIF-1α binding site; 3) attenuation of IL-8 expression by both HIF-1α small interfering RNA and R59949; 4) augmentation of IL-8 expression by either transfection with HIF-prolyl hydroxylase-2 small interfering RNA or overexpression of HIF-1α; and 5) chromatin immunoprecipitation analysis. Moreover, conditioned medium from hypoxia-treated endothelial cells augmented chemotaxis of neutrophils, due to release of IL-8. These data indicate that hypoxia-induced signaling in vascular endothelium for transcriptional activation of IL-8 involves PI3K/Akt, p38 MAPK, and HIF-1α. Pharmacological agents, which inhibit HIF-1α, may possibly ameliorate inflammation associated with hypoxia in pathological diseases.

show abstract

“…We measured the concentration of BK at the selected time points (12,14,48, and 72 hours) to decide the exposure period of A549 cells to BK and determined the levels of BK in the supernatant fluids to estimate the half-life of BK. BK was measured by a highly sensitive radioimmunoassay as previously reported.…”

Section: Measurement Of Bk Concentration In A549 Cell Culturementioning

confidence: 99%

Bradykinin Stimulates Type II Alveolar Cells to Release Neutrophil and Monocyte Chemotactic Activity and Inflammatory Cytokines

Koyama

Sato

Nomura

et al. 1998

The American Journal of Pathology

View full text Add to dashboard Cite

In the present study , we evaluated the potential of bradykinin (BK) to induce the release of neutrophil and monocyte chemotactic activity (NCA and MCA) and cytokines from an alveolar type II epithelial cell line , A549 cells. BK stimulated A549 cells to release NCA and MCA in a dose-and time-dependent manner (P < 0.001). Checkerboard analysis revealed that both NCA and MCA involved chemotactic and chemokinetic activity. Molecular sieve column chromatography showed three molecular weight masses ( Sequestration of peripheral blood neutrophils and monocytes within the lung is characteristic of a number of acute and chronic pulmonary diseases.

show abstract

Human Alveolar Macrophage-derived Chemotactic Factor for Neutrophils

Cited by 216 publications

References 31 publications

Characterization of a preclinical model of chronic ischemic wound

Characterization of a preclinical model of chronic ischemic wound

A Novel Role of Hypoxia-Inducible Factor in Cobalt Chloride- and Hypoxia-Mediated Expression of IL-8 Chemokine in Human Endothelial Cells

Bradykinin Stimulates Type II Alveolar Cells to Release Neutrophil and Monocyte Chemotactic Activity and Inflammatory Cytokines

Contact Info

Product

Resources

About