Platelets are essential for leukocyte recruitment in allergic inflammation.
BACKGROUND
The role of platelets in inflammation is recognized but poorly characterized, and little is known of their interaction with leukocytes. However, platelet-leukocyte interactions have been demonstrated in cardiovascular disease, culminating in enhanced leukocyte recruitment.


OBJECTIVE
This study was undertaken to assess the possibility and potential role of similar phenomena occurring in asthmatic patients, a murine model of allergic inflammation, and in vitro adhesion studies.


METHODS
Asthmatic patients had blood taken at various time points to document the degree of leukocyte activation and the presence of platelet-leukocyte aggregates through FACS analysis before and after allergen exposure. Similar studies were carried out in mice exposed to allergen after previous sensitization, with some groups being selectively depleted of platelets through both an immunologic (antiplatelet antiserum) and nonimmunologic (busulfan) method. Additionally, lavage fluid and airway tissue were analyzed to assess the degree of pulmonary leukocyte recruitment. The importance of platelets on leukocyte adhesion to the endothelium was then assessed with in vitro incubation of radiolabeled leukocytes in the presence of activated platelets on cultured human vascular endothelial cells.


RESULTS
We have observed circulating platelet-leukocyte aggregates in the blood of allergic asthmatic patients during the allergen-induced late asthmatic response and in sensitized mice after allergen exposure. In platelet-depleted mice infiltration of leukocytes into airways after allergen challenge was significantly reduced and could be restored by means of infusion of platelets from allergic animals, indicating an essential role for platelets in leukocyte recruitment. CD11b expression on leukocytes involved in aggregates with platelets, although not on free leukocytes, was upregulated. Furthermore, the presence of autologous platelets augmented the adhesion of human polymorphonuclear leukocytes to cultured vascular endothelial cells, an effect that was found to be endothelial cell dependent and to involve platelet activation.


CONCLUSIONS
These results suggest that platelet participation in cell recruitment occurs at the level of the circulation and might involve the priming of leukocytes for subsequent adhesion and transmigration into tissues.
Pitchford
Simon C
SC
Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, King's College London, London.
Yano
Hiroshi
H
Lever
Rebecca
R
Riffo-Vasquez
Yanira
Y
Ciferri
Silvia
S
Rose
Mark J
MJ
Giannini
Silvia
S
Momi
Stefania
S
Spina
Domenico
D
O'connor
Brian
B
Gresele
Paolo
P
Page
Clive P
CP
D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D039481:CD11b Antigen / Q000032:analysis; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000209:etiology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism
D000485:Allergens; D039481:CD11b Antigen; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010047:Ovalbumin; D009195:Peroxidase