Platelets Promote Eosinophil Adhesion of Patients with Asthma to Endothelium under Flow Conditions

Abstract

During the late-phase asthmatic response, eosinophils migrate to the bronchial tissue and cause severe damage. In this study we compared in vivo primed eosinophils from patients with allergic asthma with eosinophils from healthy control subjects in their adhesion behavior to tumor necrosis factor-alpha-activated endothelium under flow conditions (0.8 dyn/cm2). More eosinophils from patients with asthma adhered to activated endothelium, compared with cells from healthy control subjects (1,237 +/- 126 versus 887 +/- 94 cells/mm2, respectively). In the presence of blocking antibodies directed against very late antigen-4 and E-selectin, the residual binding of the cells of individuals with allergic asthma was significantly higher than that of the healthy control subjects (353 +/- 64 versus 123 +/- 31 cells/mm2, respectively, P < 0.02). In addition, secondary tethering or formation of clusters of the eosinophils of patients with allergic asthma was significantly increased compared with the healthy control subjects (cluster indices 1.8 +/- 0.3 versus 0.8 +/- 0.2, respectively, P < 0.05). Because patient cells showed an enhanced interaction with platelets during the perfusions, the role of P-selectin on platelets was investigated. Blocking antibodies directed against P-selectin reduced the enhanced binding and clustering of eosinophils of patients with allergic asthma. We conclude that P-selectin-bearing platelets contribute to secondary tethering processes of eosinophils to activated endothelium. Therefore, platelets might play an important role in the chronic inflammatory processes of these patients.

Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation

“…16 Similarly, in human asthma, platelets enhance endothelial attachment of eosinophils. 30 Thus, it could be argued that thombocytopenic animals are not subjected to tissue damage in the first instance. Evidence suggests that remodeling processes were totally inhibited in mice depleted of CD4 ϩ T lymphocytes, as was the development of inflammation in a model of chronic lung inflammation.…”

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

“…This phenomenon requires intact platelets expressing mediators on the cell surface, and in common with the occurrence of leukocyte recruitment in inflammatory diseases, platelet Pselectin is of particular importance (Diacovo et al, 1996a, b;Schober et al, 2002;Huo et al, 2003;Pitchford et al, 2005). With regard to asthma, this mechanism has been confirmed by various in vitro studies, revealing eosinophil attachment to inflamed endothelium is greatly enhanced in the presence of platelets taken from asthmatic patients, and P-selectin expressed by platelets is responsible for platelet-eosinophil interactions in particular (Jawien et al, 2002;Ulfman et al, 2003). Circulating leukocytes attached to platelets display significant increases in CD11b and very late antigen-4 integrin (VLA-4) expression, compared to leukocytes not attached to platelets, and circulating platelet-leukocyte complexes in non-inflamed animals (Pitchford et al, 2005).…”

Asthma and coagulation

“…61 Furthermore, in an in vitro flow model, more eosinophils from patients with asthma adhered to activated endothelium than eosinophils from healthy controls, a process that was dependent on platelets and P-selectin. 62 Platelets have also been shown to contribute to chronic consequences of asthma: airway wall remodeling failed to occur in allergensensitized mice depleted of platelets. 63 Platelets have been detected in BAL fluid of allergen-challenged mice 63 and extravascularly in bronchial tissue and in the intra-alveolar space in patients with asthma, 64 indicating diapedesis of platelets in areas of allergic inflammation and suggesting that platelets can contribute to lung inflammation via mechanisms that are independent of leukocytes.…”