Acute inflammation induced by immune complexes in the microcirculation.
The aims of the studies presented in this publication were to elucidate the morphology and quantitate the kinetics of an inflammatory reaction elicited by immune complexes and to ascertain the role of complement in the reaction. The hallmark of both the direct active (DAA) and reversed passive (RPA) Arthus reactions was the accumulation of immune precipitates and polymorphonuclear leukocytes (PMNs) in and around vessels. Using fluoresceinated antigen as a tracer, immune complexes localized in the lumina and walls of venules and small veins in the DAA and in the wall of vessels and perivascularly in RPA. PMNs accumulated at these same sites, phagocytosed the fluoresceinated complexes and became degranulated. The precise localization of immune complexes was achieved by examining the same tissue sections first by fluorescence microscopy, followed by conventional staining and examination by light microscopy. Marked stasis of the microcirculation was observed, particularly in DAA, in which a few immune complex-containing PMNs were entrapped in a mass of densely packed red blood cells. Some edema was observed in early lesions and definitive separation of collagen fibers was noted in lesions older than 2 hr. Hemorrhage became the dominant characteristic of both types of reactions from 2 hr onward. By administering radiolabeled cells, proteins, and microspheres as a "pulse," given at various times before sacrifice, the quantitation and kinetics of the inflammatory lesions elicited by immune complexes could be elucidated. In RPA all parameters quantitated reached a peak soon after elicitation of the reaction (2-4 hr), which is in keeping with other forms of acute inflammation. In DAA there was some difficulty in assessing the quantitation because of interanimal variations and because of progression of the inflammatory lesions, as the antigen diffused peripherally from the site of its injection. Peak activities occurred in 4- to 8-hr-old lesions. These observations and a comparison of the center and periphery of the lesions, strengthen the contention that the RPA and DAA have common features and features which differ. In common are immunological mechanisms (antigen-antibody interaction and complement activation) and cellular events (polymorphonuclear leukocyte chemotaxis, phagocytosis, and release of lysosomal contents). Different features are the site of immune complex formation and its sequelae. In RPA they form primarily in the wall of venules and small veins and hence have a marked effect on increase in vessel permeability. In the DAA most of the complexes form and the leukocytes accumulate in the lumen of the same vessels.(ABSTRACT TRUNCATED AT 400 WORDS)
Crawford
J P
JP
Movat
H Z
HZ
Minta
J O
JO
Opas
M
M
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D001183:Arthus Reaction / Q000276:immunology / Q000473:pathology; D002634:Chemotaxis, Leukocyte; D003167:Complement Activation; D003182:Complement C5 / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D007700:Kinetics; D008833:Microcirculation / Q000276:immunology* / Q000473:pathology; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D011817:Rabbits; D013997:Time Factors
D000936:Antigen-Antibody Complex; D003182:Complement C5; D003165:Complement System Proteins