ENHANCED VASCULAR-PERMEABILITY AND HEMORRHAGE-INDUCING ACTIVITY OF RABBIT C5ADES ARG - PROBABLE ROLE OF POLYMORPHONUCLEAR LEUKOCYTE LYSOSOMES

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 41  (3) , 512-520
Abstract
The injection into rabbit skin of rabbit zymosan-activated plasma (ZAP) induces marked polymorphonuclear leukocyte (PMN) infiltration, a transient increase in vascular permeability (1 h) and prolonged red blood cell extravasation lasting at least 10 h. Fractionation of ZAP to identify the factor(s) responsible for these effects is described. On CM Sephadex G-25 chromatography, the majority of the leukocyte-attracting, permeability-enhancing and hemorrhage-inducing activities eluted in the high-salt fractions (0.6 M ammonium formate, 1 M NaCl pH 5.0), suggesting that this is a very basic molecule(s). The 3 activities eluted in the same fraction on Sephadex G-100, with an apparent MW of 14,000-17,000 daltons. These observations, and the previously described requirement for C5 [complement component 5] in the plasma, suggest that C5adesarg is the active factor. Experiments performed in neutropenic rabbits indicated that PMN are required for the increase in permeability and red cell extravasation. Ultrastructural studies showed extensive degenerative changes in the infiltrating PMN evident even in 1-2 h lesions. These ranged from watery cytoplasm, loss of glycogen and cell membrane to segregation and extensive extracellular lysosome release. C5adesarg-induced chemotaxis and metabolic perturbations may contribute to this rapid degeneration of the PMN, and the lysosome release from these cells may result in progressive vascular injury.