Mechanisms of immune lysis of red blood cells in vitro. I. Paroxysmal nocturnal hemoglobinuria cells.
The effect of five different reactions which activate complement (antibody activation, reduction in ionic strength, acidification, cobra venom factor (CoF) activation, and inulin activation) upon normal and PNH cells was investigated, using normal serum and serum devoid of the fourth component of complement (C4) activity from patients with hereditary angioneurotic edema (HANE) as a source of complement. Both normal and HANE serum lysed paroxysmal nocturnal hemoglobinuria (PNH) cells when complement was activated by acidification, CoF and inulin, indicating that the terminal steps of complement were activated in the absence of C4, presumably by the alternate or properdin pathway. Normal but not HANE serum lysed cells coated with anti-I, indicating that complement was activated by the C1-dependent classic pathway. HANE serum partially supported lysis by serum at reduced ionic strength, indicating that the activation of terminal complement components had occurred through both of the pathways of activation. The amount of the third component of human complement (C3) which was bound to the membrane of lysed and unlysed cells by these procedures was determined by anti-C3 absorption and was found to differ for each method of complement activation. In general, more C3 was bound to lysed cells than to unlysed cells. For given conditions, more was bound to PNH cells than to normal cells. However, very much less bound C3 was required for lysis of the PNH cells than for lysis of normal cells. These two phenomena, especially the latter, account for the marked lysis of PNH cells when complement is activated. Normal cells treated with AET (aminoethylisothiouronium bromide) did not bind more C3 than untreated cells and the lysed cells had less bound C3 than lysed PNH cells.
D000799:Angioedema / Q000097:blood; D001665:Binding Sites; D002462:Cell Membrane; D002478:Cells, Cultured; D003168:Complement Fixation Tests; D003165:Complement System Proteins; D004912:Erythrocytes / Q000276:immunology*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000175:diagnosis; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007444:Inulin / Q000494:pharmacology; D011485:Protein Binding; D014688:Venoms; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology
D014688:Venoms; D000338:beta-Aminoethyl Isothiourea; D007444:Inulin; D003165:Complement System Proteins