Anaphylaxis-induced mesenteric vascular permeability, granulocyte adhesion, and platelet aggregates in rat.
This study investigates the response of small venules to IgE-dependent, antigen-mediated mast cell activation. Intravital microscopy was utilized to visualize 25- to 40-micron mesenteric venules, mast cell degranulation (on-line detection), vascular permeability changes (albumin leakage), leukocyte adhesion, and the formation of platelet aggregates in rats sensitized with 10 microg of intraperitoneal egg albumin (EA) in saline- or sham-sensitized (saline alone) rats. Sensitized rats challenged with EA (1 mg/ml superfusing mesentery), but not sensitized rats challenged with BSA or sham-sensitized rats challenged with EA, exhibited mast cell degranulation with significant time-dependent increases in vascular permeability (inhibited by diphenhydramine, salbutamol, and indomethacin), leukocyte adhesion (inhibited by Web-2086), and the formation of cellular aggregates (platelet), which were associated with intermittent obstruction of venular flow. Anti-platelet antibody, but not anti-neutrophil antibody or fucoidin (selectin antagonist), prevented platelet aggregate formation. Compound 48/80-induced mast cell degranulation caused similar changes in permeability (via different mediators) and leukocyte adhesion but did not induce platelet aggregation. EA-induced platelet aggregation was not inhibited by any of the mediators tested, and platelets isolated from sensitized rats failed to aggregate in response to direct EA challenge, suggesting release of an unidentified inflammatory mediator as the factor initiating platelet aggregation.
Gastrointestinal and Immunology Research Groups, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
G D
GD
Withers
P
P
Kubes
G
G
Ibbotson
R B
RB
Scott
D000420:Albuterol / Q000494:pharmacology; D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D004155:Diphenhydramine / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology*; D007073:Immunoglobulin E; D007213:Indomethacin / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology; D008784:Methysergide / Q000494:pharmacology; D018715:Microscopy, Video; D010047:Ovalbumin; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D012710:Serum Albumin, Bovine; D013152:Splanchnic Circulation / Q000276:immunology / Q000502:physiology*; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology; D014699:Venules / Q000276:immunology / Q000502:physiology / Q000503:physiopathology*
D001381:Azepines; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D004155:Diphenhydramine; D010047:Ovalbumin; D000420:Albuterol; D007213:Indomethacin; D008784:Methysergide