Immune complexes mediate rapid alterations in microvascular permeability: roles for neutrophils, complement, and platelets.
OBJECTIVE
Immune complex-induced responses involve multiple cellular and molecular mechanisms. However, how these pathways interact in the initiation of immune complex-induced response is poorly understood. Therefore the aim of this study was to investigate the immediate response of the microvasculature to immune complex formation.


METHODS
The reverse passive Arthus (RPA) model was applied to the mouse cremaster muscle. Intravital microscopy was used to examine alterations in florescein isothiocyanate (FITC)-dextran leakage from microvessels, and endothelial interactions of leukocytes and platelets in postcapillary venules.


RESULTS
Immune complex deposition induced rapid increases in microvascular permeability and leukocyte adhesion and emigration. Inhibition of platelet-activating factor (PAF) and leukotrienes inhibited the increase in permeability. Depletion of C3 reduced immune complex-mediated leukocyte recruitment and permeability, and a similar effect on permeability was observed following inhibition of leukocyte adhesion. Mast cell stabilization reduced increases in leukocyte adhesion and emigration but accelerated the increase in microvascular permeability. Platelet-endothelial interactions also increased during the RPA response, and platelet depletion delayed the changes in permeability and inhibited leukocyte recruitment.


CONCLUSIONS
This study demonstrates that immune complexes induce a rapid induction of complement-dependent leukocyte recruitment, and neutrophil-dependent microvascular dysfunction. Furthermore, this study identifies a role for platelets in promoting immune complex-induced leukocyte recruitment.
Lister
Karyn J
KJ
Centre for Inflammatory Diseases, Monash University, Victoria, Australia.
James
Will G
WG
Hickey
Michael J
MJ
D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology*; D002199:Capillary Permeability; D002450:Cell Communication; D002634:Chemotaxis, Leukocyte; D003165:Complement System Proteins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology; D007962:Leukocytes / Q000502:physiology; D051379:Mice; D018715:Microscopy, Video; D018482:Muscle, Skeletal; D009504:Neutrophils / Q000502:physiology*
D000936:Antigen-Antibody Complex; D003165:Complement System Proteins