Augmentation of Allergic Early-Phase Reaction by Nerve Growth Factor

Abstract

The allergic early-phase reaction, a hallmark of allergic bronchial asthma, is caused by allergen and immunoglobulin E-dependent mediator release from mast cells. It was previously shown that nerve growth factor (NGF) contributes to acute airway inflammation. This study further investigates the role of NGF in the allergic early-phase reaction using a well-established mouse model of ovalbumin-induced allergic airway inflammation. Treatment of sensitized and aerosol challenged BALB/c mice with blocking anti-NGF antibodies inhibited allergen-induced early-phase reaction and suppressed airway inflammation. Transgenic mice constitutively overexpressing NGF in the airways (Clara-cell secretory protein promoter [CCSP]-NGF-tg) were employed and compared with wild-type animals. In sensitized and challenged CCSP-NGF-tg mice, early-phase reaction, airway inflammation, as well as percental relative increases in serotonin levels were augmented compared with wild-type mice. These effects were paralleled by increased serotonin levels in the airways, whereas immunoglobulin E levels remained unaffected. Furthermore, CCSP-NGF-tg mice developed an increased reactivity of sensory neurons in response to inhaled capsaicin demonstrating NGF-mediated neuronal plasticity. These data provide evidence for the functional role of NGF in the development of allergic early phase responses in the airways and the lung.

Nerve growth factor is associated with islet graft failure following intraportal transplantation

“…The reason for this unexpected result remains unclear. Several studies have shown that NGF seems to have not just an islet regulatory role [19][20][21][22] but also pro-inflammatory properties, [27][28][29][30] mediating effects such as lymphocyte [31][32][33][34][35] and macrophage activation, 32,36,37 eosinophil chemotaxis, 38 and mast cell survival and degranulation. 39 One possible explanation for the discrepancy in our results is that NGF-treated islets may stimulate immunocompetent cells after intraportal islet transplantation.…”

“…45 As described above, several studies suggest that NGF can activate immunocompetent cells such as lymphocytes, macrophages and granulocytes. [27][28][29][30][31][32][33][34][35][36][37][38][39] Although several reports show the relationship between VEGF and inflammation, 46,47 to our knowledge there is no compelling evidence that VEGF directly activates immunocompetent cells. This difference in pro-inflammatory properties of growth factors might be one of the reasons for the discrepancy in transplant outcome.…”

Expression and Role of the TrkA Receptor in Pulmonary Inflammatory Diseases

“…Only one study by Ehrhard and co-workers clearly demonstrates involvement of the TrkA receptor in NGF-induced activation of T lymphocytes in vitro (Ehrhard et al, 1994). In vivo, NGF effects on T lymphocytes remain controversial, since two studies conducted in a mouse model of asthma failed to show NGF-related effects on T cells (Braun et al, 1998;Path et al, 2002). However, in a transgenic mouse tissue-specifically overexpressing NGF in the lung, increased numbers of T lymphocytes have been shown in the lung after allergenic challenge (Quarcoo et al, 2004).…”

“…In a mouse model of asthma, NGF inhibition induced by blocking antibodies administered in vivo decreases airway inflammation (Braun et al, 1998;Path et al, 2002). On the contrary, allergen sensitization and challenge in a transgenic mouse tissue specifically overexpressing NGF in the lung displays greater airway inflammation (Path et al, 2002;Quarcoo et al, 2004).…”

“…On the contrary, allergen sensitization and challenge in a transgenic mouse tissue specifically overexpressing NGF in the lung displays greater airway inflammation (Path et al, 2002;Quarcoo et al, 2004). In vivo administration of a pan-Trk receptor decoy in a mouse model of asthma reduces interleukin-(IL-)4 and IL-5 cytokine levels (Nassenstein et al, 2006).…”