Mediators of inflammation in leukocyte lysosomes. II. Mechanism of action of lysosomal cationic protein upon vascular permeability in the rat.
The vascular permeability-increasing action of rabbit PMNL lysosomes has been studied in skin and cremaster muscle of the rat. Both an extract of frozen-thawed granules and a cathepsin-free cationic protein fraction of the granules (which had previously been demonstrated to cause leukocyte adhesion and emigration in vivo) induce increased vascular permeability in skin and muscle which resembles that produced by histamine or histamine-liberators with respect to the timing of the response and the predominant type of microvessel affected. Extracts of frozen-thawed lysosomes and the inflammatory lysosomal cationic protein both cause disruption of rat mesenteric mast cells in vitro, whereas a granule-free cytoplasmic fraction of PMN leukocytes and a non-inflammatory cationic protein fraction of the granules do not do so under identical test conditions. The mastocytolytic action of lysosomal materials in vitro is not inhibited in the presence of 10 kallikrein-inhibiting units of trasylol per ml. The mast cell rupturing fraction of PMNL granules (cationic protein) possesses no detectable peroxidase activity or acid-mucopolysaccharase activity. When compared with compound 48/80 on the basis of estimated molecular weight, the lysosomal cationic protein appears to be at least as active as the latter compound with respect to in vitro mastocytolytic potency. Chronic pretreatment of rats with an agent known to reduce tissue mast cell numbers causes marked suppression of the vascular permeability change normally induced in skin and muscle by lysosomal extracts and cationic protein. Similar results are obtained if lysosomal materials are tested in rats pretreated with an antihistaminic. These observations are discussed with respect to the mode of action of PMNL lysosomes in the early and late phases of local tissue-injury reactions.
D000818:Animals; D002199:Capillary Permeability; D004396:Coloring Agents; D005615:Freezing; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006967:Hypersensitivity; D066298:In Vitro Techniques; D007249:Inflammation; D007962:Leukocytes; D008247:Lysosomes; D008407:Mast Cells; D009132:Muscles; D010544:Peroxidases; D011506:Proteins; D011817:Rabbits; D051381:Rats; D012867:Skin; D013393:Sucrase; D003189:p-Methoxy-N-methylphenethylamine
D004396:Coloring Agents; D006634:Histamine H1 Antagonists; D011506:Proteins; D003189:p-Methoxy-N-methylphenethylamine; D010544:Peroxidases; D013393:Sucrase