The Journal of Immunology, 2004, 172: 3235-3242.
Copyright © 2004 by The American Association of Immunologists
Direct In Vivo Monitoring of Acute Allergic Reactions in Human Conjunctiva1
Maaret Helintö2,*,
,¶,
Risto Renkonen
,
,¶,
Timo Tervo*,
Minna Vesaluoma*,
Heikki Saaren-Seppälä*,
Tari Haahtela
and
Juha Kirveskari
,
,||
* Department of Ophthalmology,
Helsinki University Central Hospital Laboratory Diagnostics, and
Department of Allergy, Helsinki University Central Hospital, Helsinki, Finland;
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland;
¶ Rational Drug Design Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; and
|| MediCel, Helsinki, Finland
Immediate allergic reactions are initiated by allergen-induced, specific IgE-mediated mast cell degranulation and involve leukocyte recruitment into the inflamed site. We compared conjunctival signs, symptoms, and in vivo leukocyte rolling and extravasation into sites of inflammation in five patients allergic to birch pollen and in 10 nonallergic controls who received a challenge to birch allergen or histamine. Both the specific allergen in allergic patients and histamine, both in patients and in healthy controls, induced symptoms and signs of an immediate allergic reaction together with leukocyte rolling within the conjunctival blood vessels. However, only allergen, not histamine, caused leukocyte extravasation into the site of inflammation in the allergic patients. Allergen also increased expression of endothelial P-selectin in conjunctival vessels and slowed the rolling of leukocytes which is required for their extravasation from blood circulation into the target tissue. Finally, i.v. heparin strongly reduced the number of slowly rolling cells during allergen- or histamine-induced reactions and this can probably hinder the leukocyte extravasation after allergen exposure. These findings suggest that slow rolling is required for leukocyte extravasation in acute allergic reactions, and it can be inhibited by heparin in vivo in therapeutically relevant conditions.
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