Figure 9.

Model of the development of P2Y₂R, scuPA, and PAI activity during HCPS (alveolus image was adapted from Kumar et al., 2015). Macrophages and dendritic cells recognize hantavirus after inhalation. Extracellular nucleotides increase under inflammatory conditions and activate P2 receptor family subtypes, including P2X₇ and P2Y₂R (Hechler and Gachet, 2015). Activation of P2X₇ stimulates the release of IL-1β and upregulates P2Y₂R in myeloid and endothelial cells. P2Y₂R promotes, SNV infectivity, monocyte adherence to endothelial cells through VCAM-1 and contributes to chemotaxis. TNFα primarily by myeloid lineage cells and IFN-γ released by lymphocytes during HCPS (Mori et al., 1999; Safronetz et al., 2014) have been shown to upregulate soluble uPAR and expression of membrane-bound uPAR. Thus increased expression of uPAR and uPA is expected to enhance the proteolytic activity of chemotactic cells during HCPS. PAI-1 binds poorly to scuPA-uPAR complexes and might induce appositive feedback loop for increased protease activity.