Platelet Dynamics following Allergen Challenge in Allergic Asthmatics

Abstract

Background: There is evidence that platelet activation occurs in allergic inflammation and asthma, but little is known about the role platelets play in airway inflammation associated with asthma. Objectives: In the present study, we have investigated the kinetics of platelet activation following allergen provocation of allergic asthmatics to determine the dynamics of platelet activation relative to changes in lung function and changes in airway inflammation. Methods: Changes in platelet count and haematocrit from baseline were measured during the early asthmatic response (EAR), late asthmatic response (LAR; or at corresponding time points) and at 24 h were compared between allergen- and saline-challenged groups. A subgroup of allergen-challenged asthmatics, a group of 7 challenged asthmatics and 7 controls were bronchoscoped, and BAL fluid was collected and analysed for levels of histamine and eosinophil cationic protein. Results: There was a fall in circulating platelet count, but not haematocrit after allergen challenge when compared with saline during the LAR or at 24 h. At 24 h FEV₁ had returned to within 20% of baseline in all subjects, although the thrombocytopaenia and airway inflammation persisted. Conclusions: Our results suggest that persistent thrombocytopaenia accompanies allergen exposure and persists beyond changes in airway obstruction at a time when airway inflammation is present. Our results provide further evidence that platelets may be involved in allergic disease.

The role of platelets in the pathophysiology of asthma

“…According to Taytard et al [60], a portion of the platelet population in asthmatics has a significantly reduced survival time. Recent observations also suggest a persistent, partial thrombocytopenia in allergen challenged asthmatics [61], a feature that is particularly evident in asthmatics exhibiting a late asthmatic response (LAR) 3 to 8 hours after Dermatophagoides pteronyssinus challenge [62]. This supports data indicating platelet sequestration in the bronchial circulation of challenged atopic asthmatics [63].…”

Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation

“…2 The presence of intravascular platelet aggregates within bronchial biopsy specimens in patients with asthma has also been reported. 3 Substantial clinical evidence demonstrates intravascular platelet activation accompanying allergen-induced bronchoconstriction in patients with asthma, suggestive of participation of these blood elements in the pathophysiology of asthma, [4][5][6][7][8] and the expression of P-selectin on platelets was found to be increased in patients with asthma. 9 This is also apparent in other diseases with a substantial inflammatory component, including atherosclerosis, 10 and in tumor metastasis, a disease process with many similarities to leukocyte recruitment, 11,12 the implication being that platelet activation is a general feature of diseases in which leukocyte recruitment from the circulation to particular anatomic sites is required.…”

RhoA signaling through platelet P2Y1 receptor controls leukocyte recruitment in allergic mice

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Significantly, platelet activation, as measured by changes in platelet volume, presence of platelet microparticles, and release of platelet-specific inflammatory mediators [3][4][5][6][7][8][9][10][11][12][13] ; pulmonary platelet recruitment and accumulation in the lungs 6,14,15 ; and an increased incidence of circulating platelet-leukocyte (including eosinophil) complexes, 16,17 has been recorded in asthmatic patients after spontaneous asthma attacks or allergen challenge. Furthermore, platelet activation correlates strongly to changes in lung function.…”

“…Furthermore, platelet activation correlates strongly to changes in lung function. 3,5,6,10,11,17 Of pertinence to allergy, platelets from patients allergic to Dermatophagoides pteronyssinus have been shown to be activated by the allergen or by synthetic peptides derived from the allergen through a process mediated by IgE. 18,20 Therefore these studies argue that platelet activation in the context of asthma and allergy is not a consequence of the inflammatory mediator milieu per se but rather that platelets are integral to allergic and IgE-dependent processes.…”