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 induced by parasite products occurs in malaria disease. To further elucidate the role of Plasmodium falciparum-derived products on host immune activation, we studied the expression of leukocyte adhesion molecules (CD11b/CD18 and LAM-1) on neutrophils and monocytes in response to malaria pigment using flow cytometry. Exposure of leukocytes to isolated malaria pigment derived from ruptured schizonts resulted in significant up-regulation of CD11b/CD18 expression and down-regulation of LAM-1 on both neutrophils and monocytes. In contrast, culture supernatants (pigment free) from ruptured schizonts did not alter the expression of CD11b/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 pigment on leukocyte adhesion molecules was inhibited by EDTA in a dose-dependent manner. Phagocytosis of malaria pigment was also suppressed by EDTA. This observation suggests that phagocytosis of malaria pigment may be a prerequisite for the effect of malaria pigment on the regulation of CD11b/CD18 and LAM-1 expression. Regulation of leukocyte adhesion molecules through up-regulation of CD11b/CD18 and down-regulation of LAM-1 by malaria pigment could promote leukocyte adherence to endothelium in vivo. This increased adherence of malaria pigment-activated leukocytes might induce cytokine (tumor necrosis factor alpha and interleukin-1beta)-mediated increases in capillary permeability resulting in local tissue edema, and a cytokine-mediated increase in adhesion molecule expression causing vascular clogging by adherent red blood cells, and in severe disease by adherent leukocytes.
Pichyangkul
S
S
Department of Immunology and Parasitology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Saengkrai
P
P
Yongvanitchit
K
K
Heppner
D G
DG
Kyle
D E
DE
Webster
H K
HK
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism*; D015536:Down-Regulation; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010860:Pigments, Biological / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000737:chemistry*; D015854:Up-Regulation
D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D010860:Pigments, Biological; D019041:L-Selectin; D004492:Edetic Acid