Endothelial-Leukocyte Interaction in Severe Malaria: Beyond the Brain

Figure 1

Blood barrier differences between brain and lung during malaria. (a) Cerebral microvasculature and (b) lung microvasculature without leucocytes attached in postcapillary venules and EC expressing Ang-1, under physiological conditions. (c) During severe malaria, we observe production of proinflammatory cytokines, increase of cellular adhesion molecules expression, release of Ang-2, decrease of NO, and adhesion of iRBC and leukocytes (mainly mononuclear cells) to brain vasculature leading to capillary congestion, BBB dysfunction, and edema. Such events activate the subjacent tissue (microglial cells and astrocytes). (d) Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) associated with malaria. The augment of inflammatory cytokines and chemokines, release of Ang-2, and decrease of NO are responsible for activation of EC that increases the expression of cellular adhesion molecules allowing the margination and infiltration of iRBC, leucocytes, and platelets into blood vessels, interstitial tissue, and consequently alveolar air space. BBB: blood-brain barrier; BAB: blood-air barrier; EC: endothelial cell; ROS: reactive oxygen species; SMC: smooth muscle cell.