Upregulation of expression of platelet-derived growth factor and its receptor in pneumonia associated with SHIV-infected macaques.

BACKGROUND

HIV-associated pulmonary disorders are the most frequent cause of AIDS-related deaths. Rhesus macaques infected with SIV-HIV (SHIV) recapitulate the human HIV-1 lung disease and provide an excellent working model to study the pathogenesis of the human syndrome. Lungs of macaques with SHIV-associated pneumonia have pathology involving macrophage and T cell infiltration that is often accompanied with concurrent opportunistic infections.

OBJECTIVE

To explore the relationship between SHIV-associated respiratory disease and the expression of platelet-derived growth factor (PDGF) B chain (PDGF-B) and its cognate receptors, PDGF-Ralpha and PDGF-Rbeta, which have been implicated in chronic inflammatory processes.

METHODS

Lung tissues from 10 SHIV-infected rhesus macaques were evaluated for pathological changes and correlation of these lesions with PDGF-B/PDGF-R expression by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry.

RESULTS

Virus-associated pneumonia was associated with virus replication in macrophages in the lungs, enhanced recruitment of macrophages and mononuclear cells into the organ, and, occasionally, fibrosis. These changes were accompanied by upregulation of PDGF-B and its cognate receptors in the diseased tissue. Confocal microscopy identified SHIV-infected macrophages as one of the major cell types expressing PDGF-B and PDGF-Ralpha/beta in the affected lungs.

CONCLUSION

These results suggest that PDGF and its cognate receptors play a critical role in the pathogenesis of pulmonary disease associated with this virus.