A Critical Role for Mouse CXC Chemokine(s) in Pulmonary Neutrophilia During Th Type 1-Dependent Airway Inflammation

Abstract

Ag-specific Th1 and Th2 cells have been demonstrated to play a critical role in the induction of allergic diseases. Here we have investigated the precise mechanisms of Th1-induced airway inflammation. Airway inflammation was induced in BALB/c mice by transfer of freshly induced OVA-specific Th1 or Th2 cells followed by OVA inhalation. In this model, both Th1 and Th2 cells induced airway inflammation. The former induced neutrophilia in airways, whereas the latter induced eosinophilia. Moreover, we found that Th1 cells induced more severe airway hyperresponsiveness (AHR) than Th2 cells. The eosinophilia induced by Th2 cell infusion was almost completely blocked by administration of anti-IL-5 mAb, but not anti-IL-4 mAb. In contrast, Th1-induced AHR and pulmonary neutrophilia were inhibited by the administration of anti-human IL-8R Ab, which blocks the function of mouse CXC chemokine(s). These findings reveal a critical role of mouse CXC chemokine(s) in Th1-dependent pulmonary neutrophilia and AHR.

Inhalation of Aspergillus fumigatus spores induces airway inflammation in mice in a similar manner as observed in Recurrent Airway Obstruction in horses

“…Also, the increase in the levels of IgG2a in the BALF from mice that were exposed to allergen is compatible with a Th1 response (Takaoka et al 2001). These findings mimic the conditions typically observed in RAO-affected horses that have elevated levels of IgGa and IgGb isotypes .…”

A Potent and Selective Nonpeptide Antagonist of CXCR2 Inhibits Acute and Chronic Models of Arthritis in the Rabbit

“…This is consistent with the observed effects of our CXCR2 antagonist in human IL-8-induced joint inflammation in the rabbit. Also similar to the rabbit studies is the fact that GRO-␣(8-73) and anti-murine CXCR2 IgG were shown to effectively inhibit neutrophil recruitment induced by proinflammatory stimuli not known to act directly through CXCR2, such as LPS and Ag (OVA), respectively (71,74), supporting the notion that neutrophil recruitment by such stimuli is mediated, at least in part, via production of CXCR2 agonists.…”

Neutrophils Regulate Airway Responses in a Model of Fungal Allergic Airways Disease

“…This was surprising, because recruited neutrophils have been shown to be mediate Th-1 pattern inflammation in response to several classes of microbial pathogens (16,(67)(68)(69). In contrast, adoptive transfer of either OVA-specific Th-1 or Th-2 T cells to naive mice has been shown to result in enhanced pulmonary expression of ELR ϩ CXC chemokines and lung neutrophil influx upon exposure of the recipients to OVA (15). Taken together with our findings, this suggests that, at least in the context of airway allergy, recruited neutrophils may represent a common effector mechanism of airway inflammation in both Th-1-and Th-2-acquired immunity.…”

“…In addition, mediators of neutrophil chemotaxis, such as ELR ϩ CXC chemokines and leukotriene-B 4 , are expressed in both human allergic airway disease and animal models (12,13). The precise contribution of neutrophils to the pathogenesis of allergic airway disease is not clearly defined: given the correlation of airway neutrophilia with severity of airway obstruction in humans, neutrophils have been postulated to promote more severe airway inflammation by mediating direct tissue injury or by elaborating proinflammatory mediators (14,15). Conversely, it is possible that the accumulation of neutrophils is an epiphenomenon that does not directly contribute to pathogenesis.…”