REGULATION OF LEUKOCYTE ADHESION MOLECULES CD11B CD18 AND LEUKOCYTE ADHESION MOLECULE-1 ON PHAGOCYTIC-CELLS ACTIVATED BY MALARIA PIGMENT/

There is increasing evidence that inappropriate immune activation indu ced by parasite products occurs in malaria disease. To further elucida te the role of Plasmodium falciparum-derived products on host immune a ctivation, we studied the expression of leukocyte adhesion molecules ( CD11b/CD18 and LAM-1) on neutrophils and monocytes in response to mala ria pigment using flow cytometry. Exposure of leukocytes to isolated m alaria pigment derived from ruptured schizonts resulted in significant up-regulation of CD11b/CD18 expression and down-regulation of LAM-1 o n both neutrophils and monocytes. In contrast, culture-supernatants (p igment free) from ruptured schizonts did not alter the expression of C D11b/CD18 and LAM-1. The increase of CD11b/CD18 and the loss of LAM-1 expression occurred simultaneously with the earliest response detected at 10 min and a plateau reached by 60 min. The effect of malaria pigm ent on leukocyte adhesion molecules was inhibited by EDTA in a dose-de pendent manner. Phagocytosis of malaria pigment was also suppressed by EDTA. This observation suggests that phagocytosis of malaria pigment may be a prerequisite fcr the effect of malaria pigment on the regulat ion of CD11b/CD18 and LAM-1 expression. Regulation of leukocyte adhesi on molecules through up-regulation of CD11b/CD18 and downregulation of LAM-1 by malaria pigment could promote leukocyte adherence to endothe lium in vivo. This increased adherence of malaria pigment-activated le ukocytes might induce cytokine (tumor necrosis factor alpha and interl eukin-1 beta)-mediated increases in capillary permeability resulting i n local tissue edema, and a cytokine-mediated increase in adhesion mol ecule expression causing vascular clogging by adherent red blood cells , and in severe disease by adherent leukocytes.