S. Pichyangkul et al., REGULATION OF LEUKOCYTE ADHESION MOLECULES CD11B CD18 AND LEUKOCYTE ADHESION MOLECULE-1 ON PHAGOCYTIC-CELLS ACTIVATED BY MALARIA PIGMENT/, The American journal of tropical medicine and hygiene, 57(4), 1997, pp. 383-388
Citations number
24
Categorie Soggetti
Public, Environmental & Occupation Heath","Tropical Medicine
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.