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CXC Chemokine Receptor-2 Ligands Are Necessary Components of Neutrophil-Mediated Host Defense in Invasive Pulmonary Aspergillosis

Mehrad, Borna ; Strieter, Robert M ; Moore, Thomas A ; Tsai, Wan C ; Lira, Sergio A ; Standiford, Theodore J

The Journal of immunology (1950), 1999-12, Vol.163 (11), p.6086-6094 [Periódico revisado por pares]

United States: Am Assoc Immnol

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Título:
CXC Chemokine Receptor-2 Ligands Are Necessary Components of Neutrophil-Mediated Host Defense in Invasive Pulmonary Aspergillosis
Autor: Mehrad, Borna ; Strieter, Robert M ; Moore, Thomas A ; Tsai, Wan C ; Lira, Sergio A ; Standiford, Theodore J
Assuntos: Animals ; Aspergillosis - immunology ; Aspergillosis - mortality ; Aspergillus fumigatus ; Chemokine CXCL1 ; Chemokine CXCL2 ; Chemokines, CXC - metabolism ; Chemotactic Factors - metabolism ; Chemotaxis, Leukocyte ; CXCR2 protein ; Female ; Growth Substances - metabolism ; Immunosuppression ; Intercellular Signaling Peptides and Proteins ; Ligands ; Lung - pathology ; Lung Diseases, Fungal - immunology ; Lung Diseases, Fungal - mortality ; Mice ; Mice, Inbred C57BL ; Monokines - metabolism ; Neutrophil Infiltration ; Neutrophils - immunology ; Receptors, Chemokine - metabolism ; Receptors, Interleukin - metabolism ; Receptors, Interleukin-8B
É parte de: The Journal of immunology (1950), 1999-12, Vol.163 (11), p.6086-6094
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
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Descrição: Invasive pulmonary aspergillosis is a devastating complication of immunosuppression, which occurs in association with neutrophil dysfunction or deficiency. ELR+ CXC chemokines are a subfamily of chemokines that play a critical role in neutrophil chemotaxis and activation both in vitro and in vivo. We hypothesized that interaction of these ligands with CXC chemokine receptor-2 (CXCR2), their sole murine receptor, is a major component of neutrophil-dependent pulmonary host defense against Aspergillus fumigatus. In immunocompetent animals, neutrophils were recruited to the lung in response to intratracheally administered A. fumigatus conidia. In a model of transient in vivo depletion of neutrophils, animals developed invasive pulmonary aspergillosis, associated with delayed influx of neutrophils into the lung. In both normal and neutrophil-depleted animals, the ELR+ CXC chemokines MIP-2 and KC were induced in response to intratracheal administration of conidia. Ab-mediated neutralization of the common ELR+ CXC chemokine receptor, CXCR2, resulted in development of invasive disease indistinguishable from the disease in neutrophil-depleted animals, while control animals were highly resistant to the development of infection. CXCR2 neutralization was associated with reduced lung neutrophil influx and resulted in a marked increase in mortality compared with controls. In contrast, animals with constitutive lung-specific transgenic expression of KC were resistant to the organism, with reduced mortality and lower lung burden of fungus. We conclude that CXCR2 ligands are essential mediators of host defense against A. fumigatus, and may be important targets in devising future therapeutic strategies in this disease.
Editor: United States: Am Assoc Immnol
Idioma: Inglês

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CXC Chemokine Receptor-2 Ligands Are Necessary Components of Neutrophil-Mediated Host Defense in Invasive Pulmonary Aspergillosis

Mehrad, Borna ; Strieter, Robert M ; Moore, Thomas A ; Tsai, Wan C ; Lira, Sergio A ; Standiford, Theodore J

United States: Am Assoc Immnol

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